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1
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Jhuang JR, Lee CH, Chiang CJ, Chen CJ, Lee WC. Reduced burden of Arsenic-Related cancers after water mitigation in Taiwan. ENVIRONMENT INTERNATIONAL 2024; 185:108542. [PMID: 38461779 DOI: 10.1016/j.envint.2024.108542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 01/31/2024] [Accepted: 02/28/2024] [Indexed: 03/12/2024]
Abstract
BACKGROUND Epidemiological evidence has demonstrated an association between arsenic in drinking water and increased cancer incidence. This population-based study investigates the impact of a tap water supply system installation in Blackfoot disease-endemic regions of Taiwan on cancer incidence. METHODS By using the Taiwan Cancer Registry dataset, we enrolled patients aged 40-84 diagnosed with arsenic-related cancers, including hepatocellular carcinoma, small and squamous cell lung cancer, Bowen's disease, basal and squamous cell skin cancer, urothelial bladder cancer, and upper tract urothelial carcinoma between 1995 and 2019. Random-effects age-period-cohort models were used to estimate the cancer incidence data, and a stabilized kriging method was employed to interpolate incidence rates to more precise spatiotemporal units. RESULTS The results showed that the age-standardized incidence rates of all six types of studied cancers were consistently higher in Blackfoot disease-endemic areas than those in other areas from 1995 to 2019. However, the gap in incidence rates between Blackfoot disease-endemic areas and the remaining regions began to narrow approximately after the 1960 birth cohort when the tap water supply system installation commenced. For small and squamous cell lung cancer, Bowen's disease, and urothelial bladder cancer, the excess incidence rates sharply declined to null for those born after the year of arsenic mitigation. For upper tract urothelial carcinoma, the excess incidence rates decreased more gradually for those born after the year of arsenic mitigation. For hepatocellular carcinoma and basal and squamous cell skin cancer, the excess incidence rates remained constant. Spatiotemporal clusters of high incidence rates were identified in the core townships of Blackfoot disease-endemic areas. These clusters began to dissipate mainly after the 1960 birth cohort. CONCLUSION Arsenic mitigation from drinking water in Taiwan is associated with a reduced burden of small and squamous cell lung cancers, Bowen's disease, urothelial bladder cancer, and upper tract urothelial carcinoma.
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Affiliation(s)
- Jing-Rong Jhuang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Taiwan Cancer Registry, Taipei, Taiwan
| | - Chih-Hung Lee
- Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Ju Chiang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Taiwan Cancer Registry, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; College of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan
| | - Wen-Chung Lee
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Taiwan Cancer Registry, Taipei, Taiwan; Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
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Yin F, Zhang Y, Zhang X, Zhang M, Zhang Z, Yin Y, Xu H, Yang Y, Gao Y. The ROS/NF-κB/HK2 axis is involved in the arsenic-induced Warburg effect in human L-02 hepatocytes. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024; 34:150-165. [PMID: 36264688 DOI: 10.1080/09603123.2022.2134559] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/04/2022] [Indexed: 06/16/2023]
Abstract
Arsenic has been identified as a carcinogen, although the molecular mechanism underlying itscarcinogenesis has not been fully elucidated. To date, only a few studies have attempted to confirm a direct link between oxidative stress and the Warburg effect . This study demonstrated that 0.2 μmol/L As3+ induced the Warburg effect to contribute to abnormal proliferation of L-02 cells, that was mediated by upregulation of hexokinase 2 (HK2), a key enzyme in glycolysis. Further study indicated that arsenic-induced accumulation of reactive oxygen species (ROS) activated the nuclear factor kappa B (NF-κB) signaling pathway by phosphorylation of p65 at the Ser536 and Ser276 sites, leading to upregulated expression of HK2. We therefore concluded that the ROS/NF-κB/HK2 axis contributes to the Warburg effect and cell proliferation induced by low doses of arsenic.AbbreviationsROS, Reactive oxygen species; NAC, N-acetyl-L-cysteine; 2-DG, 2-deoxy-D-glucose; 2-NBDG, 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose.
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Affiliation(s)
- Fanshuo Yin
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China
| | - Ying Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China
| | - Xin Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China
| | - Meichen Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China
| | - Zaihong Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China
| | - Yunyi Yin
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China
| | - Haili Xu
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
- Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China
| | - Yanmei Yang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
| | - Yanhui Gao
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China
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Lin MH, Li CY, Cheng YY, Guo HR. Arsenic in Drinking Water and Incidences of Leukemia and Lymphoma: Implication for Its Dual Effects in Carcinogenicity. Front Public Health 2022; 10:863882. [PMID: 35570949 PMCID: PMC9099091 DOI: 10.3389/fpubh.2022.863882] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 04/08/2022] [Indexed: 01/11/2023] Open
Abstract
Arsenic in drinking water has been recognized as carcinogenic to humans and can cause solid cancers of lung, urinary bladder, and skin. Positive associations have also been reported between arsenic ingestion and cancers of kidney, liver and prostate. Nevertheless, arsenic trioxide has been used successfully in the treatment of acute promyelocytic leukemia. Therefore, arsenic might play different roles in the carcinogenesis of solid cancers and hematologic malignancies. The relationship between arsenic in drinking water and the incidences of hematologic malignancies has not been fully investigated. We established a cohort of Taiwanese population and assorted 319 townships of Taiwan into two exposure categories using 0.05 mg/L as the cutoff. Then, we linked these data to the Taiwan Cancer Registry and computed standardized incidence ratios (SIRs) of lymphoma and leukemia by sex, exposure category and time period. The trend of changes in the SIRs over time was assessed, from 1981-1990 to 1991-2000 and then to 2001-2010. We found that in both lymphoma and leukemia, the higher exposure category was associated with lower SIRs in both men and women. In terms of time trends, the SIRs in both lymphoma and leukemia showed increasing trends in both sexes, while exposure to arsenic in drinking water decreased over time. The arsenic level in drinking water was negatively associated with the incidences of lymphoma and leukemia in both men and women. This study supports the dual effects of arsenic on carcinogenesis, with a potential protective effect against hematologic malignancies.
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Affiliation(s)
- Ming-Hsien Lin
- Division of Hematology and Oncology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan,Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ya-Yun Cheng
- Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, Boston, MA, United States
| | - How-Ran Guo
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan,Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan,*Correspondence: How-Ran Guo
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Yeh H, Chiang CC, Yen TH. Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges. World J Gastroenterol 2021; 27:4104-4142. [PMID: 34326614 PMCID: PMC8311541 DOI: 10.3748/wjg.v27.i26.4104] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/17/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.
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Affiliation(s)
- Hsuan Yeh
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
| | - Chun-Cheng Chiang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
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Zhao R, Wang B, Guo Y, Zhang J, Chen D, He WM, Zhao YJ, Ding Y, Jin C, Li C, Zhao Y, Ren W, Fang L. Quantitative proteomics reveals arsenic attenuates stem-loop binding protein stability via a chaperone complex containing heat shock proteins and ERp44. Proteomics 2021; 21:e2100035. [PMID: 34132035 DOI: 10.1002/pmic.202100035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 05/25/2021] [Accepted: 06/04/2021] [Indexed: 12/25/2022]
Abstract
Arsenic pollution impacts health of millions of people in the world. Inorganic arsenic is a carcinogenic agent in skin and lung cancers. The stem-loop binding protein (SLBP) binds to the stem-loop of the canonical histone mRNA and regulates its metabolism during cell cycle. Our previous work has shown arsenic induces ubiquitin-proteasome dependent degradation of SLBP and contributes to lung cancer. In this study, we established the first comprehensive SLBP interaction network by affinity purification-mass spectrometry (AP-MS) analysis, and further demonstrated arsenic enhanced the association between SLBP and a crucial chaperone complex containing heat shock proteins (HSPs) and ERp44. Strikingly, knockdown of these proteins markedly rescued the protein level of SLBP under arsenic exposure conditions, and abolished the increasing migration capacity of BEAS-2B cells induced by arsenic. Taken together, our study provides a potential new mechanism that a chaperone complex containing HSPs and ERp44 attenuates the stability of SLBP under both normal and arsenic exposure conditions, which could be essential for arsenic-induced high cell migration.
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Affiliation(s)
- Ruoyu Zhao
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China.,The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Binghao Wang
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China
| | - Yan Guo
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China
| | - Jingzi Zhang
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China
| | - Danqi Chen
- Department of Environmental Medicine & Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA
| | - Wei Ming He
- State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
| | - Yong Juan Zhao
- State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
| | - Yibing Ding
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China
| | - Chunyuan Jin
- Department of Environmental Medicine & Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA
| | - Chaojun Li
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China
| | - Yue Zhao
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China
| | - Wei Ren
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Lei Fang
- Jiangsu Key Laboratory of Molecular Medicine, Medical School & Chemistry and Biomedicine Innovation Center of Nanjing University, Nanjing, China
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Monteiro De Oliveira EC, Caixeta ES, Santos VSV, Pereira BB. Arsenic exposure from groundwater: environmental contamination, human health effects, and sustainable solutions. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2021; 24:119-135. [PMID: 33709865 DOI: 10.1080/10937404.2021.1898504] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Arsenic (As) occurs naturally in geologic conditions, but groundwater contamination might also be found due to the consequences of mining, agricultural and industrial processes. Human exposure to As after drinking contaminated water is commonly associated with acute toxicity outcomes and chronic effects ranging from skin lesions to cancer. Integrated actions from environmental and health authorities are needed to reduce exposure, monitoring outcomes, and promotion of actions to offer sustainable As-safe water alternatives. Considering recent research trends, the present review summarizes and discusses current issues associated with the process and effects of contamination and decontamination in an environmental health perspective. Recent findings reinforce the harmful effects of the consumption of As-contaminated water and broaden the scope of related diseases including intestinal maladies, type 2 diabetes, cancers of bladder, kidneys, lung, and liver. Among the main strategies to diminish or remove As from water, the following are highlighted (1) ion exchange system and membrane filtration (micro, ultra, and nanofiltration) as physicochemical treatment systems; (2) use of cyanobacteria and algae in bioremediation programs and (3) application of nanotechnology for water treatment.
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Affiliation(s)
| | - Evelyn Siqueira Caixeta
- Department of Genetics and Biochemistry, Federal University of Uberlândia, Institute of Biotechnology, Uberlândia, Minas Gerais, Brazil
| | - Vanessa Santana Vieira Santos
- Department of Genetics and Biochemistry, Federal University of Uberlândia, Institute of Biotechnology, Uberlândia, Minas Gerais, Brazil
| | - Boscolli Barbosa Pereira
- Department of Genetics and Biochemistry, Federal University of Uberlândia, Institute of Biotechnology, Uberlândia, Minas Gerais, Brazil
- Institute of Geography, Department of Environmental Health, Federal University of Uberlândia, Santa Mônica Campus, Uberlândia, Minas Gerais, Brazil
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Navarro-Espinoza S, Angulo-Molina A, Meza-Figueroa D, López-Cervantes G, Meza-Montenegro M, Armienta A, Soto-Puebla D, Silva-Campa E, Burgara-Estrella A, Álvarez-Bajo O, Pedroza-Montero M. Effects of Untreated Drinking Water at Three Indigenous Yaqui Towns in Mexico: Insights from a Murine Model. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18020805. [PMID: 33477870 PMCID: PMC7832869 DOI: 10.3390/ijerph18020805] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 12/18/2022]
Abstract
Background: Reports in a northwestern Mexico state linked arsenic (As) in drinking water to DNA damage in people from indigenous communities. However, this correlation remains under discussion due to unknown variables related to nutrition, customs, and the potential presence of other metal(oid)s. Methods: To determine this association, we sampled water from three Yaqui towns (Cócorit, Vícam, and Pótam), and analyzed the metals by ICP-OES. We exposed four separate groups, with five male CD-1 mice each, to provide further insight into the potential effects of untreated drinking water. Results: The maximum concentrations of each metal(oid) in µg·L−1 were Sr(819) > Zn(135) > As(75) > Ba(57) > Mo(56) > Cu(17) > Al(14) > Mn(12) > Se(19). Histological studies revealed brain cells with angulation, satellitosis, and reactive gliosis with significant statistical correlation with Mn and As. Furthermore, the liver cells presented hepatocellular degeneration. Despite the early response, there is no occurrence of both statistical and significative changes in hematological parameters. Conclusions: The obtained results provide experimental insights to understand the potential effects of untreated water with low As and Mn contents in murine models. This fact is noteworthy because of the development of histological changes on both the brain and liver at subchronic exposure.
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Affiliation(s)
- Sofia Navarro-Espinoza
- Department of Geology, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico;
| | - Aracely Angulo-Molina
- Department of Biological Chemical Sciences, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico;
- Department of Physics Research, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico; (D.S.-P.); (E.S.-C.); (A.B.-E.); (O.Á.-B.)
| | - Diana Meza-Figueroa
- Department of Geology, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico;
- Correspondence: (D.M.-F.); (M.P.-M.)
| | - Guillermo López-Cervantes
- Department of Medicine, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico;
| | - Mercedes Meza-Montenegro
- Department of Natural Resources, Sonora Technological Institute, 5 de Febrero 818 Sur, Obregon City 85000, Sonora, Mexico;
| | - Aurora Armienta
- Institute of Geophysics, National Autonomous University of Mexico-UNAM, Coyoacán 04510, Ciudad de Mexico, Mexico;
| | - Diego Soto-Puebla
- Department of Physics Research, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico; (D.S.-P.); (E.S.-C.); (A.B.-E.); (O.Á.-B.)
| | - Erika Silva-Campa
- Department of Physics Research, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico; (D.S.-P.); (E.S.-C.); (A.B.-E.); (O.Á.-B.)
| | - Alexel Burgara-Estrella
- Department of Physics Research, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico; (D.S.-P.); (E.S.-C.); (A.B.-E.); (O.Á.-B.)
| | - Osiris Álvarez-Bajo
- Department of Physics Research, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico; (D.S.-P.); (E.S.-C.); (A.B.-E.); (O.Á.-B.)
- Consejo Nacional de Ciencia y Tecnología CONACyT, Insurgentes 1582, Benito Juárez 03940, Ciudad de Mexico, Mexico
| | - Martín Pedroza-Montero
- Department of Physics Research, University of Sonora, Rosales and Encinas, Hermosillo 83000, Sonora, Mexico; (D.S.-P.); (E.S.-C.); (A.B.-E.); (O.Á.-B.)
- Correspondence: (D.M.-F.); (M.P.-M.)
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Hasanvand M, Mohammadi R, Khoshnamvand N, Jafari A, Palangi HS, Mokhayeri Y. Dose-response meta-analysis of arsenic exposure in drinking water and intelligence quotient. JOURNAL OF ENVIRONMENTAL HEALTH SCIENCE & ENGINEERING 2020; 18:1691-1697. [PMID: 33312671 PMCID: PMC7721833 DOI: 10.1007/s40201-020-00570-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 10/15/2020] [Indexed: 05/11/2023]
Abstract
OBJECTIVES Exposure to inorganic arsenic through drinking water is a threat for public health. Using the arsenic-containing water in the long-term causes a variety of skin diseases, high blood pressure, and skin cancer. Arsenic also damages the nervous system. A wide range of studies have studied the effect of arsenic in drinking water on the level of intelligence in children. METHODS For the purpose of our research, we searched three electronic databases including Scopus, Web of Science, and Medline (PubMed) in English from 2000 to January 2018. We used the dose-response meta-analysis through applying random effect models in order to estimate the pooled association (with a 95% uncertainty) between water arsenic concentration and intelligence level. RESULTS Using a two-stage random effect model to investigate the dose-response association between arsenic concentration and Intelligence Quotient scale, we estimated a significant linear association as -0.08 (95% CI: -0.14, -0.01). Actually, for each unit increase in arsenic concentration (one microgram per liter), intelligence quotient scale decreases by 0.08%. CONCLUSIONS Considering the significance of the relationship between arsenic concentration in drinking water and the level of intelligence quotient as an important factor in training, the level of arsenic and its associated risks should be decreased in water resources.
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Affiliation(s)
- Mahsa Hasanvand
- Department of Environmental Health Engineering, School of Public Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Rasool Mohammadi
- Department of Epidemiology and Biostatistics, School of Public Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Nahid Khoshnamvand
- Department of Environmental Health Engineering, School of Public Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
- Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Jafari
- Department of Environmental Health Engineering, School of Public Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
| | | | - Yaser Mokhayeri
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
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9
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Berardozzi E, Tuninetti JS, Einschlag FSG, Azzaroni O, Ceolín M, Rafti M. Comparison of Arsenate Adsorption from Neutral pH Aqueous Solutions Using Two Different Iron-Trimesate Porous Solids: Kinetics, Equilibrium Isotherms, and Synchrotron X-Ray Absorption Experiments. J Inorg Organomet Polym Mater 2020. [DOI: 10.1007/s10904-020-01774-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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10
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Zuzolo D, Cicchella D, Demetriades A, Birke M, Albanese S, Dinelli E, Lima A, Valera P, De Vivo B. Arsenic: Geochemical distribution and age-related health risk in Italy. ENVIRONMENTAL RESEARCH 2020; 182:109076. [PMID: 31901628 DOI: 10.1016/j.envres.2019.109076] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 11/11/2019] [Accepted: 12/20/2019] [Indexed: 06/10/2023]
Abstract
This study is the first attempt to evaluate occurrence, distribution and potential health impacts of As at a national scale in Italy. In various environmental matrices, As geochemical distribution was investigated and carcinogenic and non-carcinogenic risks were assessed with respect to different exposure routes and age groups. Both deterministic and probabilistic methods were used to determine the health risks. Geochemical mapping at a sub-continental scale provided a useful tool to spatially represent As concentration and the critical areas posing a health threat to inhabitants. The results show that significant As concentrations in tap water and soil (up to 27.20 μg/l and 62.20 mg/kg, respectively) are mainly governed by geological features. In the central parts of Italy, where alkaline volcanic materials and consequently high levels of As occur, the residents are prone to health issues. Daily exposure to As in tap water is unparalleled playing an important role in the potential cancer and non-cancer risks. The Incremental Lifetime Cancer Risk for skin cancer and also lung and bladder cancer associated with tap water ingestion interestingly shows that (i) almost 80% of the computed values fall above the internationally accepted benchmark value of 1 × 10-5; (ii) majority of the data exceed the acceptable risk proposed by most jurisdictions, such as that of Italian law (1 × 10-6). Further, geographical variation of health risk highlights high carcinogenic and non-carcinogenic risk associated with water ingestion for those living in the northern Alps (including the city of Trento) and the central and southern Italy (including the capital Rome and the cities of Napoli and Catanzaro). According to the results, application of the probabilistic method which considers variability and uncertainty is preferred to the deterministic approach for risk assessment. The sensitivity analysis showed that As concentration in drinking water and exposure duration are the factors with the greatest impact on the outcome of risk assessment (for all age groups). The results of the current study may be a good starting point for authorities to urgently decide about the needed policy actions in order to prevent the adverse health effects and to reduce the human health risk due to As exposure.
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Affiliation(s)
- Daniela Zuzolo
- Department of Science and Technology, University of Sannio, 82100, Benevento, Italy.
| | - Domenico Cicchella
- Department of Science and Technology, University of Sannio, 82100, Benevento, Italy
| | - Alecos Demetriades
- Institute of Geology and Mineral Exploration (retired), 1 Spirou Louis St., Olympic Village, 136 77, Acharnae, Athens, Hellas, Greece
| | - Manfred Birke
- Federal Institute for Geosciences and Natural Resources, Stilleweg 2, 30655, Hannover, Germany
| | - Stefano Albanese
- Department of Earth Sciences, Environment and Resources, University of Napoli "Federico II", 80125, Napoli, Italy
| | - Enrico Dinelli
- Department of Biological, Geological and Environmental Sciences, University of Bologna, 40100, Bologna, Italy
| | - Annamaria Lima
- Department of Earth Sciences, Environment and Resources, University of Napoli "Federico II", 80125, Napoli, Italy
| | - Paolo Valera
- Department of Civil-Environmental Engineering and Architecture, University of Cagliari, 09123, Cagliari, Italy
| | - Benedetto De Vivo
- Norwest Italia Srl, 80138, Napoli, Italy; Pegaso University, 80132, Napoli, Italy
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11
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Zhang H, Wang L, Wang Y, Chang S. Using disability-adjusted life years to estimate the cancer risks of low-level arsenic in drinking water. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART A, TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING 2019; 55:63-70. [PMID: 31538532 DOI: 10.1080/10934529.2019.1667167] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 09/03/2019] [Accepted: 09/04/2019] [Indexed: 06/10/2023]
Abstract
Recent studies have shown that long-term exposure to low-level arsenic (<10 μg/L) may cause human health problems. However, the induced cancer risks and differences among multisite cancers have not been well-understood. In this study, the concentrations of low-level arsenic in drinking water in XP city, Northwest China were investigated. A health risk assessment was carried out for different age groups and exposure pathways based on Monte Carlo simulations and disability-adjusted life years (DALYs). The measured arsenic levels were in the range of 7.61-9.25 μg/L with a mean of 8.23 μg/L. For the public, the average total lifetime cancer risk was 3.87 × 10-4, and the total DALYs estimation for all age groups was 20.58 person-year. The average individual DALYs lost was 3.35 × 10-5 per person-year (ppy), which was 33.5 times the reference value (1.00 × 10-6 ppy). The mortality burden had a considerably larger contribution (97.31%) to the total disease burden, and the 60-65-year age group exhibited the largest DALYs lost. Skin cancer exhibited the largest burden of 2.15 × 10-5 ppy, followed by lung cancer (1.20 × 10-5 ppy). This study might be useful for potential strategies of risk control and management in XP drinking water.
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Affiliation(s)
- Hui Zhang
- Key Laboratory of Northwest Resource, Environment and Ecology, MOE, Xi'an University of Architecture and Technology, Xi'an, China
- Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an, China
| | - Luobin Wang
- Key Laboratory of Northwest Resource, Environment and Ecology, MOE, Xi'an University of Architecture and Technology, Xi'an, China
- Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an, China
| | - Yiyi Wang
- Key Laboratory of Northwest Resource, Environment and Ecology, MOE, Xi'an University of Architecture and Technology, Xi'an, China
- Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an, China
| | - Shan Chang
- Key Laboratory of Northwest Resource, Environment and Ecology, MOE, Xi'an University of Architecture and Technology, Xi'an, China
- Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an, China
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12
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Costa M. Review of arsenic toxicity, speciation and polyadenylation of canonical histones. Toxicol Appl Pharmacol 2019; 375:1-4. [PMID: 31077704 DOI: 10.1016/j.taap.2019.05.006] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 05/01/2019] [Accepted: 05/07/2019] [Indexed: 12/14/2022]
Abstract
Arsenic contamination impacts hundreds of millions of people in the world. Arsenic is a well-established human carcinogen and has been shown to cause skin, lung, bladder, liver, prostate and kidney cancers, in humans. Mechanisms that underlie arsenic-mediated carcinogenesis, including epigenetic alterations, remain largely unknown. Human exposure to Arsenic is reviewed, and the mechanisms of its acute and chronic toxicity and mechanisms of its carcinogenesis in humans are discussed. Arsenic is one of the few metals that is metabolized in vivo, and Arsenic methylation and how this results in a shorter half-life in vivo are discussed. A review of recent findings that Arsenic causes loss in the cellular levels of Stem Loop Binding Protein (SLBP) resulting in polyadenylation of canonical histones (H3.1) as a default, increasing levels of H3.1 protein outside of S-Phase. Malignant cell transformation is induced by knockdown of SLBP and by overexpression of polyadenylated H3.1. Arsenic induced polyadenylation of H3.1 causes enhanced levels of H3.1 protein displacing H3.3 protein from its cellular binding sites, since the two proteins differ by only 5 amino acids. Knockdown of H3.3 alone can induce carcinogenesis, and therefore displacement of functional H3.3 protein by increased H3.1 protein, is likely a mechanism of arsenic carcinogenesis.
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Affiliation(s)
- Max Costa
- Department of Environmental Medicine, New York University School of Medicine, 341 East 25th Street, New York, NY 10100, United States of America.
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13
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Saint-Jacques N, Brown P, Nauta L, Boxall J, Parker L, Dummer TJB. Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada. ENVIRONMENT INTERNATIONAL 2018; 110:95-104. [PMID: 29089168 DOI: 10.1016/j.envint.2017.10.014] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 09/18/2017] [Accepted: 10/20/2017] [Indexed: 05/04/2023]
Abstract
Arsenic in drinking water impacts health. Highest levels of arsenic have been historically observed in Taiwan and Bangladesh but the contaminant has been affecting the health of people globally. Strong associations have been confirmed between exposure to high-levels of arsenic in drinking water and a wide range of diseases, including cancer. However, at lower levels of exposure, especially near the current World Health Organization regulatory limit (10μg/L), this association is inconsistent as the effects are mostly extrapolated from high exposure studies. This ecological study used Bayesian inference to model the relative risk of bladder and kidney cancer at these lower concentrations-0-2μg/L; 2-5μg/L and; ≥5μg/L of arsenic-in 864 bladder and 525 kidney cancers diagnosed in the study area, Nova Scotia, Canada between 1998 and 2010. The model included proxy measures of lifestyle (e.g. smoking) and accounted for spatial dependencies. Overall, bladder cancer risk was 16% (2-5μg/L) and 18% (≥5μg/L) greater than that of the referent group (<2μg/L), with posterior probabilities of 88% and 93% for these risks being above 1. Effect sizes for kidney cancer were 5% (2-5μg/L) and 14% (≥5μg/L) above that of the referent group (<2μg/L), with probabilities of 61% and 84%. High-risk areas were common in southwestern areas, where higher arsenic-levels are associated with the local geology. The study suggests an increased bladder cancer, and potentially kidney cancer, risk from exposure to drinking water arsenic-levels within the current the World Health Organization maximum acceptable concentration.
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Affiliation(s)
- Nathalie Saint-Jacques
- Nova Scotia Cancer Care Program, Nova Scotia Health Authority, 1276 South Park Street, Room 560 Bethune Building, Halifax B3H 2Y9, Nova Scotia, Canada.
| | - Patrick Brown
- Centre for Global Health Research, St. Michael's Hospital, 30 Bond Street, Toronto M5B 1W8, Ontario, Canada.
| | - Laura Nauta
- Population Cancer Research Program, Dalhousie University, 1494 Carlton Street, PO Box 15000, Halifax B3H 4R2, Nova Scotia, Canada.
| | - James Boxall
- GIS Centre Killam Library, Dalhousie University, 6225 University Avenue, Halifax B3H 4R2, Nova Scotia, Canada.
| | - Louise Parker
- Department of Pediatrics and Population Cancer Research Program, Dalhousie University, 1494 Carlton Street, PO Box 15000, Halifax B3H 4R2, Nova Scotia, Canada.
| | - Trevor J B Dummer
- The University of British Columbia, Centre for Excellence in Cancer Prevention, School of Population and Public Health, 2206 East Mall, Vancouver V6T 1Z3, British Columbia, Canada.
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14
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Chen B, Lu X, Arnold LL, Cohen SM, Le XC. Identification of Methylated Dithioarsenicals in the Urine of Rats Fed with Sodium Arsenite. Chem Res Toxicol 2016; 29:1480-7. [DOI: 10.1021/acs.chemrestox.6b00151] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Baowei Chen
- MOE Key Laboratory
of Aquatic Product Safety, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510275, People’s Republic of China
- Analytical and Environmental Toxicology Division, Department
of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2G3, Canada
- South China Sea Resource Exploitation and Protection Collaborative
Innovation Center, Sun Yat-Sen University, Guangzhou 510275, People’s Republic of China
| | - Xiufen Lu
- Analytical and Environmental Toxicology Division, Department
of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2G3, Canada
| | - Lora L. Arnold
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, United States
| | - Samuel M. Cohen
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, United States
| | - X. Chris Le
- Analytical and Environmental Toxicology Division, Department
of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2G3, Canada
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15
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Shim J, Kennedy RH, Weatherly LM, Hutchinson LM, Pelletier JH, Hashmi HN, Blais K, Velez A, Gosse JA. Arsenic inhibits mast cell degranulation via suppression of early tyrosine phosphorylation events. J Appl Toxicol 2016; 36:1446-59. [PMID: 27018130 DOI: 10.1002/jat.3300] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 12/18/2015] [Accepted: 01/05/2016] [Indexed: 12/22/2022]
Abstract
Exposure to arsenic is a global health concern. We previously documented an inhibitory effect of inorganic Arsenite on IgE-mediated degranulation of RBL-2H3 mast cells (Hutchinson et al., 2011; J. Appl. Toxicol. 31: 231-241). Mast cells are tissue-resident cells that are positioned at the host-environment interface, thereby serving vital roles in many physiological processes and disease states, in addition to their well-known roles in allergy and asthma. Upon activation, mast cells secrete several mediators from cytoplasmic granules, in degranulation. The present study is an investigation of Arsenite's molecular target(s) in the degranulation pathway. Here, we report that arsenic does not affect degranulation stimulated by either the Ca(2) (+) ionophore A23187 or thapsigargin, which both bypass early signaling events. Arsenic also does not alter degranulation initiated by another non-IgE-mediated mast cell stimulant, the G-protein activator compound 48/80. However, arsenic inhibits Ca(2) (+) influx into antigen-activated mast cells. These results indicate that the target of arsenic in the degranulation pathway is upstream of the Ca(2) (+) influx. Phospho-Syk and phospho-p85 phosphoinositide 3-kinase enzyme-linked immunosorbent assays data show that arsenic inhibits early phosphorylation events. Taken together, this evidence indicates that the mechanism underlying arsenic inhibition of mast cell degranulation occurs at the early tyrosine phosphorylation steps in the degranulation pathway. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Juyoung Shim
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA
| | - Rachel H Kennedy
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA.,Graduate School of Biomedical Science and Engineering, University of Maine, Orono, Maine, 04469, USA
| | - Lisa M Weatherly
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA.,Graduate School of Biomedical Science and Engineering, University of Maine, Orono, Maine, 04469, USA
| | - Lee M Hutchinson
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA
| | - Jonathan H Pelletier
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA
| | - Hina N Hashmi
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA
| | - Kayla Blais
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA
| | - Alejandro Velez
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA
| | - Julie A Gosse
- Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine, 04469, USA. .,Graduate School of Biomedical Science and Engineering, University of Maine, Orono, Maine, 04469, USA.
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16
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Arsenic Exposure and Immunotoxicity: a Review Including the Possible Influence of Age and Sex. Curr Environ Health Rep 2016; 3:1-12. [DOI: 10.1007/s40572-016-0082-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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17
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Brocato J, Chen D, Liu J, Fang L, Jin C, Costa M. A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA. Biol Trace Elem Res 2015; 166:72-81. [PMID: 25893362 PMCID: PMC4470754 DOI: 10.1007/s12011-015-0296-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 03/03/2015] [Indexed: 12/27/2022]
Abstract
Canonical histones are synthesized with a peak in S-phase, whereas histone variants are formed throughout the cell cycle. Unlike messenger RNA (mRNA) for all other genes with a poly(A) tail, canonical histone mRNAs contain a stem-loop structure at their 3'-ends. This stem-loop structure is the binding site for the stem-loop binding protein (SLBP), a protein involved in canonical histone mRNA processing. Recently, we found that arsenic depletes SLBP by enhancing its proteasomal degradation and epigenetically silencing the promoter of the SLBP gene. The loss of SLBP disrupts histone mRNA processing and induces aberrant polyadenylation of canonical histone H3.1 mRNA. Here, we present new data supporting the idea that the lack of SLBP allows the H3.1 mRNA to be polyadenylated using the downstream poly(A) signal. SLBP was also depleted in arsenic-transformed bronchial epithelial cells (BEAS-2B), which led us to hypothesize the involvement of SLBP and polyadenylated H3.1 mRNA in carcinogenesis. Here, for the first time, we report that overexpression of H3.1 polyadenylated mRNA, and knockdown of SLBP enhances anchorage-independent cell growth. A pcDNA-H3.1 vector with a poly(A) signal sequence was stably transfected into BEAS-2B cells. Polyadenylated H3.1 mRNA and exogenous H3.1 protein levels were significantly increased in cells containing the pcDNA-H3.1 vector. A soft agar assay revealed that cells containing the vector formed significantly higher numbers of colonies compared to wild-type cells. Moreover, small hairpin RNA for SLBP (shSLBP) was used to knockdown the expression of SLBP. Cells stably transfected with the shSLBP vector grew significantly more colonies in soft agar than cells transfected with a control vector. These data suggest that upregulation of polyadenylated H3.1 mRNA holds potential as a mechanism to facilitate carcinogenesis by toxicants such as arsenic that depletes SLBP.
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Affiliation(s)
- Jason Brocato
- Department of Environmental Medicine, NYU School of Medicine, NY, NY, 10016 USA
| | - Danqi Chen
- Department of Environmental Medicine, NYU School of Medicine, NY, NY, 10016 USA
| | - Jianli Liu
- Department of Environmental Medicine, NYU School of Medicine, NY, NY, 10016 USA
| | - Lei Fang
- Department of Environmental Medicine, NYU School of Medicine, NY, NY, 10016 USA
| | - Chunyuan Jin
- Department of Environmental Medicine, NYU School of Medicine, NY, NY, 10016 USA
| | - Max Costa
- Department of Environmental Medicine, NYU School of Medicine, NY, NY, 10016 USA
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18
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Tanase AM, Marchio A, Dumitrascu T, Dima S, Herlea V, Oprisan G, Dejean A, Popescu I, Pineau P. Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome. JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY 2015; 25:256-263. [PMID: 24736102 DOI: 10.1038/jes.2014.16] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Revised: 12/06/2013] [Accepted: 01/10/2014] [Indexed: 06/03/2023]
Abstract
Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To date, HCC from this country has not been subject to molecular characterization. We analyzed a series of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and the mitochondrial D-loop. Oxidative stress response was monitored through measurement of gene expression (NRF2, KEAP1, SRXN1, and CES1) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for β-catenin and NRF2 (P<0.0001). Besides, tumors from patients born in Greater Bucharest carried TP53 mutations more frequently than others (45 vs 10%, P=0.02). Finally, a R249S mutation of TP53, well-known hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore, that distinct mutagenic processes affect Romanian patients with HCC. Further analyses are now warranted in order to identify causal lifestyle or environmental factors.
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Affiliation(s)
- Anna-Maria Tanase
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Sos. Fundeni, Bucharest, Romania
| | - Agnès Marchio
- Unité d'Organisation Nucléaire et Oncogenèse, INSERM U993, Institut Pasteur, rue du Docteur Roux, Paris, France
| | - Traian Dumitrascu
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Sos. Fundeni, Bucharest, Romania
| | - Simona Dima
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Sos. Fundeni, Bucharest, Romania
| | - Vlad Herlea
- Department of Pathology, Fundeni Clinical Institute, Sos. Fundeni, Bucharest, Romania
| | - Gabriela Oprisan
- Molecular Biology Laboratory, National Institute for Research/Development of Microbiology and Immunology Cantacuzino, Splaiul Independentei, Bucharest, Romania
| | - Anne Dejean
- Unité d'Organisation Nucléaire et Oncogenèse, INSERM U993, Institut Pasteur, rue du Docteur Roux, Paris, France
| | - Irinel Popescu
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Sos. Fundeni, Bucharest, Romania
| | - Pascal Pineau
- Unité d'Organisation Nucléaire et Oncogenèse, INSERM U993, Institut Pasteur, rue du Docteur Roux, Paris, France
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19
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20
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Huang L, Wu H, van der Kuijp TJ. The health effects of exposure to arsenic-contaminated drinking water: a review by global geographical distribution. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2014; 25:432-452. [PMID: 25365079 DOI: 10.1080/09603123.2014.958139] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Chronic arsenic exposure through drinking water has been a vigorously studied and debated subject. However, the existing literature does not allow for a thorough examination of the potential regional discrepancies that may arise among arsenic-related health outcomes. The purpose of this article is to provide an updated review of the literature on arsenic exposure and commonly discussed health effects according to global geographical distribution. This geographically segmented approach helps uncover the discrepancies in the health effects of arsenic. For instance, women are more susceptible than men to a few types of cancer in Taiwan, but not in other countries. Although skin cancer and arsenic exposure correlations have been discovered in Chile, Argentina, the United States, and Taiwan, no evident association was found in mainland China. We then propose several globally applicable recommendations to prevent and treat the further spread of arsenic poisoning and suggestions of future study designs and decision-making.
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Affiliation(s)
- Lei Huang
- a State Key Laboratory of Pollution Control & Resource Reuse , School of the Environment, Nanjing University , Nanjing , China
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21
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Nacano LR, de Freitas R, Barbosa F. Evaluation of seasonal dietary exposure to arsenic, cadmium and lead in schoolchildren through the analysis of meals served by public schools of Ribeirão Preto, Brazil. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2014; 77:367-374. [PMID: 24617541 DOI: 10.1080/15287394.2013.874874] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Dietary exposure to arsenic (AS), cadmium (Cd), and lead (Pb) of Brazilian schoolchildren living in Ribeirão Preto, Brazil, was assessed. Food samples including rice, beans, vegetables, fruits, and meat served daily by public schools were collected as presented in different seasons. Metallic elements were determined by inductively coupled plasma-mass spectrometry (ICP-MS).The main sources of As, Cd, and Pb were found to be rice, vegetables, and pork, respectively. Further, in some food types there were seasonal differences in the concentrations of metallic elements. The mean daily intakes of As, Cd, and Pb based upon the association between food consumption data and the observed concentrations of metals in their diet were 6.9 μg, 0.9 μg, and 0.6 μg for As, Cd, and Pb, respectively. These findings are below the toxicological reference values provided by the European Food Safety Authority (EFSA) and the World Health Organization (WHO).
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Affiliation(s)
- Letícia Ramos Nacano
- a Laboratório de Toxicologia e Essencialidade de Metais, Faculdade de Ciências Farmacêuticas de Ribeirão Preto , Universidade de São Paulo, Monte Alegre , Ribeirão Preto , São Paulo , Brazil
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Lin HJ, Sung TI, Chen CY, Guo HR. Arsenic levels in drinking water and mortality of liver cancer in Taiwan. JOURNAL OF HAZARDOUS MATERIALS 2013; 262:1132-1138. [PMID: 23352725 DOI: 10.1016/j.jhazmat.2012.12.049] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2012] [Revised: 08/11/2012] [Accepted: 12/27/2012] [Indexed: 06/01/2023]
Abstract
The carcinogenic effect of arsenic is well documented, but epidemiologic data on liver cancer were limited. To evaluate the dose-response relationship between arsenic in drinking water and mortality of liver cancer, we conducted a study in 138 villages in the southwest coast area of Taiwan. We assessed arsenic levels in drinking water using data from a survey conducted by the government and reviewed death certificates from 1971 to 1990 to identify liver cancer cases. Using village as the unit, we conducted multi-variate regression analyses and then performed post hoc analyses to validate the findings. During the 20-year period, 802 male and 301 female mortality cases of liver cancer were identified. After adjusting for age, arsenic levels above 0.64 mg/L were associated with an increase in the liver cancer mortality in both genders, but no significant effect was observed for lower exposure categories. Post hoc analyses and a review of literature supported these findings. We concluded that exposures to high arsenic levels in drinking water are associated with the occurrence of liver cancer, but such an effect is not prominent at exposure levels lower than 0.64 mg/L.
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Affiliation(s)
- Hung-Jung Lin
- Cancer Research Center, Chi-Mei Medical Center, Tainan, Taiwan; Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan; Graduate Institute of Injury Prevention and Control, College of Public Health and Nutrition, Taipei Medical University, Taipei,Taiwan
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Dufey F, Walsh L, Sogl M, Tschense A, Schnelzer M, Kreuzer M. Radiation dose dependent risk of liver cancer mortality in the German uranium miners cohort 1946-2003. JOURNAL OF RADIOLOGICAL PROTECTION : OFFICIAL JOURNAL OF THE SOCIETY FOR RADIOLOGICAL PROTECTION 2013; 33:175-185. [PMID: 23295324 DOI: 10.1088/0952-4746/33/1/175] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
An increased risk of mortality from primary liver cancers among uranium miners has been observed in various studies. An analysis of the data from a German uranium miner cohort (the 'Wismut cohort') was used to assess the relationship with ionising radiation. To that end the absorbed organ dose due to high and low linear energy transfer radiation was calculated for 58 987 miners with complete information on radiation exposure from a detailed job-exposure matrix. 159 deaths from liver cancer were observed in the follow-up period from 1946 to 2003. Relative risk models with either linear or categorical dependence on high and low linear energy transfer radiation liver doses were fitted by Poisson regression, stratified on age and calendar year. The linear trend of excess relative risk in a model with both low and high linear transfer radiation is -0.8 (95% confidence interval (CI): -3.7, 2.1) Gy(-1) and 48.3 (95% CI: -32.0, 128.6) Gy(-1) for low and high linear energy transfer radiation, respectively, and thus not statistically significant for either dose. The increase of excess relative risk with equivalent liver dose is 0.57 (95% CI: -0.69, 1.82) Sv(-1). Adjustment for arsenic only had a negligible effect on the radiation risk. In conclusion, there is only weak evidence for an increase of liver cancer mortality with increasing radiation dose in the German uranium miners cohort considered. However, both a lack of statistical power and potential misclassification of primary liver cancer are issues.
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Affiliation(s)
- F Dufey
- Department Radiation Protection and Health, Federal Office for Radiation Protection, Ingolstädter Landstrasse 1, D-85764 Oberschleissheim, Germany.
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Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA. The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. ENVIRONMENTAL HEALTH PERSPECTIVES 2013; 121:295-302. [PMID: 23458756 PMCID: PMC3621177 DOI: 10.1289/ehp.1205875] [Citation(s) in RCA: 852] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2012] [Accepted: 12/21/2012] [Indexed: 05/17/2023]
Abstract
BACKGROUND Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. OBJECTIVES We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. METHODS We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. DISCUSSION Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. CONCLUSIONS These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.
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Chervona Y, Hall MN, Arita A, Wu F, Sun H, Tseng HC, Ali E, Uddin MN, Liu X, Zoroddu MA, Gamble MV, Costa M. Associations between arsenic exposure and global posttranslational histone modifications among adults in Bangladesh. Cancer Epidemiol Biomarkers Prev 2012; 21:2252-60. [PMID: 23064002 PMCID: PMC3518638 DOI: 10.1158/1055-9965.epi-12-0833] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Exposure to arsenic (As) is associated with an increased risk of several cancers as well as cardiovascular disease, and childhood neuro-developmental deficits. Arsenic compounds are weakly mutagenic, alter gene expression and posttranslational histone modifications (PTHMs) in vitro. METHODS Water and urinary As concentrations as well as global levels of histone 3 lysine 9 di-methylation and acetylation (H3K9me2 and H3K9ac), histone 3 lysine 27 tri-methylation and acetylation (H3K27me3 and H3K27ac), histone 3 lysine 18 acetylation (H3K18ac), and histone 3 lysine 4 trimethylation (H3K4me3) were measured in peripheral blood mononuclear cells (PBMC) from a subset of participants (N = 40) of a folate clinical trial in Bangladesh (FACT study). RESULTS Total urinary As (uAs) was positively correlated with H3K9me2 (r = 0.36, P = 0.02) and inversely with H3K9ac (r = -0.47, P = 0.002). The associations between As and other PTHMs differed in a gender-dependent manner. Water As (wAs) was positively correlated with H3K4me3 (r = 0.45, P = 0.05) and H3K27me3 (r = 0.50, P = 0.03) among females and negatively correlated among males (H3K4me3: r = -0.44, P = 0.05; H3K27me3: r = -0.34, P = 0.14). Conversely, wAs was inversely associated with H3K27ac among females (r = -0.44, P = 0.05) and positively associated among males (r = 0.29, P = 0.21). A similar pattern was observed for H3K18ac (females: r = -0.22, P = 0.36; males: r = 0.27, P = 0.24). CONCLUSION Exposure to As is associated with alterations of global PTHMs; gender-specific patterns of association were observed between As exposure and several histone marks. IMPACT These findings contribute to the growing body of evidence linking As exposure to epigenetic dysregulation, which may play a role in the pathogenesis of As toxicity.
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Affiliation(s)
- Yana Chervona
- New York University School of Medicine, Department of Environmental Medicine, New York, NY
| | - Megan N. Hall
- Departments of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
| | - Adriana Arita
- New York University School of Medicine, Department of Environmental Medicine, New York, NY
| | - Fen Wu
- New York University School of Medicine, Department of Environmental Medicine, New York, NY
| | - Hong Sun
- New York University School of Medicine, Department of Environmental Medicine, New York, NY
| | - Hsiang-Chi Tseng
- New York University School of Medicine, Department of Environmental Medicine, New York, NY
| | - Eunus Ali
- Columbia University Arsenic Project in Bangladesh
| | | | - Xinhua Liu
- Biostatistics, Mailman School of Public Health, Columbia University, New York, NY
| | | | - Mary V. Gamble
- Department of Environmental Health Sciences Mailman School of Public Health, Columbia University, New York, NY
| | - Max Costa
- New York University School of Medicine, Department of Environmental Medicine, New York, NY
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Smith AH, Marshall G, Liaw J, Yuan Y, Ferreccio C, Steinmaus C. Mortality in young adults following in utero and childhood exposure to arsenic in drinking water. ENVIRONMENTAL HEALTH PERSPECTIVES 2012; 120:1527-31. [PMID: 22949133 PMCID: PMC3556614 DOI: 10.1289/ehp.1104867] [Citation(s) in RCA: 133] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Accepted: 09/04/2012] [Indexed: 05/02/2023]
Abstract
BACKGROUND Beginning in 1958, the city of Antofagasta in northern Chile was exposed to high arsenic concentrations (870 µg/L) when it switched water sources. The exposure abruptly stopped in 1970 when an arsenic-removal plant commenced operations. A unique exposure scenario like this--with an abrupt start, clear end, and large population (125,000 in 1970), all with essentially the same exposure--is rare in environmental epidemiology. Evidence of increased mortality from lung cancer, bronchiectasis, myocardial infarction, and kidney cancer has been reported among young adults who were in utero or children during the high-exposure period. OBJECTIVE We investigated other causes of mortality in Antofagasta among 30- to 49-year-old adults who were in utero or ≤ 18 years of age during the high-exposure period. METHODS We compared mortality data between Antofagasta and the rest of Chile for people 30-49 years of age during 1989-2000. We estimated expected deaths from mortality rates in all of Chile, excluding Region II where Antofagasta is located, and calculated standardized mortality ratios (SMRs). RESULTS We found evidence of increased mortality from bladder cancer [SMR = 18.1; 95% confidence interval (CI): 11.3, 27.4], laryngeal cancer (SMR = 8.1; 95% CI: 3.5, 16.0), liver cancer (SMR = 2.5; 95% CI: 1.6, 3.7), and chronic renal disease (SMR = 2.0; 95% CI: 1.5, 2.8). CONCLUSIONS Taking together our findings in the present study and previous evidence of increased mortality from other causes of death, we conclude that arsenic in Antofagasta drinking water has resulted in the greatest increases in mortality in adults < 50 years of age ever associated with early-life environmental exposure.
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Affiliation(s)
- Allan H Smith
- Arsenic Health Effects Research Program, School of Public Health, University of California, Berkeley, Berkeley, California 94720-7360, USA.
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Chervona Y, Costa M. The control of histone methylation and gene expression by oxidative stress, hypoxia, and metals. Free Radic Biol Med 2012; 53:1041-7. [PMID: 22841757 PMCID: PMC3432141 DOI: 10.1016/j.freeradbiomed.2012.07.020] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Revised: 07/03/2012] [Accepted: 07/18/2012] [Indexed: 12/14/2022]
Abstract
The harmful consequences of carcinogenic metals, such as nickel, arsenic, and chromium, are thought to be in part due to their ability to induce oxidative stress. The ubiquity of oxidative stress in biological systems has made it a fairly obvious culprit in causing cellular damage and/or development of disease. However, the full extent of oxidative stress-induced damage is not limited to its direct effects on cellular components, such as lipids, proteins, and DNA, but may extend to its ability to alter gene expression. Gene expression regulation is an important component of cellular and/or tissue homeostasis, and its alteration can have detrimental consequences. Therefore, a growing amount of interest is being paid to understanding how oxidative stress can influence gene expression. Oxidative stress-induced epigenetic dysregulation in the form of posttranslational histone modifications, in particular, is a popular topic of research. This review will therefore primarily focus on discussing the role of oxidative stress and hypoxia on histone methylation and/or gene expression alterations. The sources of oxidative stress discussed here are carcinogenic metals, such as, nickel, arsenic, and chromium.
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Affiliation(s)
- Yana Chervona
- Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York 10987, USA
| | - Max Costa
- Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York 10987, USA
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Kim SC, Park SJ, Lee JR, Seo JC, Yang CH, Byun SH. Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 5:165-71. [PMID: 18604262 PMCID: PMC2396482 DOI: 10.1093/ecam/nem014] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2006] [Accepted: 01/16/2007] [Indexed: 11/14/2022]
Abstract
Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml(-1)) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3.
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Affiliation(s)
- Sang Chan Kim
- College of Oriental Medicine and Research Center for Biomedical Resources of Oriental Medicine, Daegu Haany University, 165 Sang-dong, Suseong-gu, Daegu 706-060, Korea
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Chervona Y, Arita A, Costa M. Carcinogenic metals and the epigenome: understanding the effect of nickel, arsenic, and chromium. Metallomics 2012; 4:619-27. [PMID: 22473328 PMCID: PMC3687545 DOI: 10.1039/c2mt20033c] [Citation(s) in RCA: 182] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Carcinogenic metals, such as nickel, arsenic, and chromium, are widespread environmental and occupational pollutants. Chronic exposure to these metals has been connected with increased risks of numerous cancers and as well as non-carcinogenic health outcomes, including cardiovascular disease, neurologic deficits, neuro-developmental deficits in childhood, and hypertension. However, currently the specific molecular targets for metal toxicity and carcinogenicity are not fully understood. Here, we propose that the iron- and 2-oxoglutarate-dependent dioxygenase family enzymes, as well as, other histone modifying enzymes are important intracellular targets that mediate the toxicity and carcinogenicity of nickel, and maybe potential targets in chromium and arsenic induced carcinogenesis. Our data demonstrate that all three metals are capable of inducing post-translational histone modifications and affecting the enzymes that modulate them (i.e. the iron- and 2-oxoglutarate-dependent dioxygenase family, including HIF-prolyl hydroxylase PHD2, histone demethylase JHDM2A/JMJD1A, and DNA repair enzymes ABH3 and ABH2, and histone methyltransferases, G9a). Given the effects that these metals can exert on the epigenome, future studies of their involvement in histone modifying enzymes dynamics would deepen our understanding on their respective toxicities and carcinogenicities.
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Affiliation(s)
- Yana Chervona
- New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987
| | - Adriana Arita
- New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987
| | - Max Costa
- New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987
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Gong G, O'Bryant SE. Low-level arsenic exposure, AS3MT gene polymorphism and cardiovascular diseases in rural Texas counties. ENVIRONMENTAL RESEARCH 2012; 113:52-57. [PMID: 22341486 DOI: 10.1016/j.envres.2012.01.003] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2011] [Revised: 12/20/2011] [Accepted: 01/04/2012] [Indexed: 05/31/2023]
Abstract
Most Americans living in rural areas use groundwater for drinking. Exposure to low-level (around the current U.S. standard 10 μg/L) arsenic in drinking water is associated with increased mortality of cardiovascular diseases. The current study was to determine if coronary heart disease, hypertension, and hyperlipidemia were associated with low-level arsenic exposure and AS3MT gene single nucleotide polymorphism (SNP) A35991G (rs10748835) in rural Texas. Subjects (156 men, 343 women, 40-96 years of age with a mean of 61) were residents from rural counties Cochran, Palmer, and Bailey, Texas. Groundwater arsenic concentration at each subject's home was estimated with ArcGIS inverse distance weighted interpolation based on the residential location's distances to surrounding wells with known water arsenic concentrations. The estimated groundwater arsenic concentration ranged from 2.2 to 15.3 (mean 6.2) μg/L in this cohort. Logistic regression analysis showed that coronary heart disease was associated with higher arsenic exposure (p<0.05) and with AS3MT genotype GG vs. AA (p<0.05) after adjustments for age, ethnicity, gender, education, smoking status, alcoholism, and anti-hyperlipidemia medication. Hypertension was associated with higher arsenic exposure, while hyperlipidemia was associated with genotype AG vs. AA of the AS3MT gene (p<0.05). Thus, coronary heart disease and its main risk factors were associated with low-level arsenic exposure, AS3MT polymorphism or both.
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Affiliation(s)
- Gordon Gong
- F. Marie Hall Institute for Rural and Community Health, Texas Tech University Health Science Center, 3601 4th Street, STOP 6232, Lubbock, TX 79430-6232, USA
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Coelho P, Costa S, Silva S, Walter A, Ranville J, Sousa ACA, Costa C, Coelho M, García-Lestón J, Pastorinho MR, Laffon B, Pásaro E, Harrington C, Taylor A, Teixeira JP. Metal(loid) levels in biological matrices from human populations exposed to mining contamination--Panasqueira Mine (Portugal). JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2012; 75:893-908. [PMID: 22788375 DOI: 10.1080/15287394.2012.690705] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Mining activities may affect the health of miners and communities living near mining sites, and these health effects may persist even when the mine is abandoned. During mining processes various toxic wastes are produced and released into the surrounding environment, resulting in contamination of air, drinking water, rivers, plants, and soils. In a geochemical sampling campaign undertaken in the Panasqueira Mine area of central Portugal, an anomalous distribution of several metals and arsenic (As) was identified in various environmental media. Several potentially harmful elements, including As, cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), and selenium (Se), were quantified in blood, urine, hair, and nails (toe and finger) from a group of individuals living near the Panasqueira Mine who were environmentally and occupationally exposed. A group with similar demographic characteristics without known exposure to mining activities was also compared. Genotoxicity was evaluated by means of T-cell receptor (TCR) mutation assay, and percentages of different lymphocyte subsets were selected as immunotoxicity biomarkers. Inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis showed elevated levels of As, Cd, Cr, Mn, and Pb in all biological samples taken from populations living close to the mine compared to controls. Genotoxic and immunotoxic differences were also observed. The results provide evidence of an elevated potential risk to the health of populations, with environmental and occupational exposures resulting from mining activities. Further, the results emphasize the need to implement preventive measures, remediation, and rehabilitation plans for the region.
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Affiliation(s)
- Patrícia Coelho
- National Institute of Health, Environmental Health Department, Porto, Portugal.
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Chen B, Arnold LL, Cohen SM, Thomas DJ, Le XC. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water. Toxicol Sci 2011; 124:320-6. [PMID: 21934131 DOI: 10.1093/toxsci/kfr246] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.
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Affiliation(s)
- Baowei Chen
- Analytical and Environmental Toxicology Division, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada
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Mitchell E, Frisbie S, Sarkar B. Exposure to multiple metals from groundwater-a global crisis: geology, climate change, health effects, testing, and mitigation. Metallomics 2011; 3:874-908. [PMID: 21766119 DOI: 10.1039/c1mt00052g] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
This paper presents an overview of the global extent of naturally occurring toxic metals in groundwater. Adverse health effects attributed to the toxic metals most commonly found in groundwater are reviewed, as well as chemical, biochemical, and physiological interactions between these metals. Synergistic and antagonistic effects that have been reported between the toxic metals found in groundwater and the dietary trace elements are highlighted, and common behavioural, cultural, and dietary practices that are likely to significantly modify health risks due to use of metal-contaminated groundwater are reviewed. Methods for analytical testing of samples containing multiple metals are discussed, with special attention to analytical interferences between metals and reagents. An overview is presented of approaches to providing safe water when groundwater contains multiple metallic toxins.
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Flora SJS. Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 2011; 51:257-81. [PMID: 21554949 DOI: 10.1016/j.freeradbiomed.2011.04.008] [Citation(s) in RCA: 551] [Impact Index Per Article: 39.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2010] [Revised: 03/18/2011] [Accepted: 04/04/2011] [Indexed: 12/12/2022]
Abstract
This review summarizes the literature describing the molecular mechanisms of arsenic-induced oxidative stress, its relevant biomarkers, and its relation to various diseases, including preventive and therapeutic strategies. Arsenic alters multiple cellular pathways including expression of growth factors, suppression of cell cycle checkpoint proteins, promotion of and resistance to apoptosis, inhibition of DNA repair, alterations in DNA methylation, decreased immunosurveillance, and increased oxidative stress, by disturbing the pro/antioxidant balance. These alterations play prominent roles in disease manifestation, such as carcinogenicity, genotoxicity, diabetes, cardiovascular and nervous systems disorders. The exact molecular and cellular mechanisms involved in arsenic toxicity are rather unrevealed. Arsenic alters cellular glutathione levels either by utilizing this electron donor for the conversion of pentavalent to trivalent arsenicals or directly binding with it or by oxidizing glutathione via arsenic-induced free radical generation. Arsenic forms oxygen-based radicals (OH(•), O(2)(•-)) under physiological conditions by directly binding with critical thiols. As a carcinogen, it acts through epigenetic mechanisms rather than as a classical mutagen. The carcinogenic potential of arsenic may be attributed to activation of redox-sensitive transcription factors and other signaling pathways involving nuclear factor κB, activator protein-1, and p53. Modulation of cellular thiols for protection against reactive oxygen species has been used as a therapeutic strategy against arsenic. N-acetylcysteine, α-lipoic acid, vitamin E, quercetin, and a few herbal extracts show prophylactic activity against the majority of arsenic-mediated injuries in both in vitro and in vivo models. This review also updates the reader on recent advances in chelation therapy and newer therapeutic strategies suggested to treat arsenic-induced oxidative damage.
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Affiliation(s)
- Swaran J S Flora
- Division of Pharmacology & Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
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Kile ML, Hoffman E, Rodrigues EG, Breton CV, Quamruzzaman Q, Rahman M, Mahiuddin G, Hsueh YM, Christiani DC. A pathway-based analysis of urinary arsenic metabolites and skin lesions. Am J Epidemiol 2011; 173:778-86. [PMID: 21378128 DOI: 10.1093/aje/kwq427] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Inorganic arsenic is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Limited evidence suggests that the ability to fully metabolize arsenic into DMA influences susceptibility to disease. To determine whether percentage of MMA was predictive of disease, the authors used data from a case-control study conducted in Bangladesh (2001-2003). Persons who were diagnosed with keratosis, melanosis, Bowen's disease, or squamous cell carcinoma were matched on age, sex, and village to persons without these conditions. This analysis was restricted to persons who had no missing data on covariates (859 cases, 868 controls). A path analysis was used to evaluate simultaneously the association between the percentage of all urinary arsenic metabolites and the odds of skin lesions using PROC CALIS in SAS, version 9.1 (SAS Institute, Inc., Cary, North Carolina) and Mplus, version 6.1 (Muthén & Muthén, Los Angeles, California). The odds of skin lesions were significantly associated with log(10) percentage of MMA (adjusted odds ratio (OR(adj)) = 1.56, 95% confidence interval (CI): 1.15, 2.12) but not log(10) percentage of inorganic arsenic (OR(adj) = 1.06, 95% CI: 0.75, 1.50) or log(10) percentage of DMA (OR(adj) = 1.07, 95% CI: 0.33, 3.46). This novel analysis confirmed that persons who excrete a higher proportion of MMA have a greater risk of skin lesions after data are adequately controlled for urinary arsenic metabolites, current arsenic exposure, and other risk factors.
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Affiliation(s)
- Molly L Kile
- Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
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Dopp E, von Recklinghausen U, Diaz-Bone R, Hirner AV, Rettenmeier AW. Cellular uptake, subcellular distribution and toxicity of arsenic compounds in methylating and non-methylating cells. ENVIRONMENTAL RESEARCH 2010; 110:435-42. [PMID: 19758587 DOI: 10.1016/j.envres.2009.08.012] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2009] [Revised: 08/10/2009] [Accepted: 08/13/2009] [Indexed: 05/25/2023]
Abstract
Arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder, liver and lung. Inorganic arsenic, existing in highly toxic trivalent and significantly less toxic pentavalent forms, is methylated to mono- and di-methylated species mainly in the liver. Due to the low toxicity of pentavalent methylated species, methylation has been regarded as a detoxification process for many years; however, recent findings of a high toxicity of trivalent methylated species have indicated the contrary. In order to elucidate the role of speciation and methylation for the toxicity and carcinogenicity of arsenic, systematic studies were conducted comparing cellular uptake, subcellular distribution as well as toxic and genotoxic effects of organic and inorganic pentavalent and trivalent arsenic species in both non-methylating (urothelial cells and fibroblasts) and methylating cells (hepatocytes). The membrane permeability was found to be dependent upon both the arsenic species and the cell type. Uptake rates of trivalent methylated species were highest and exceeded those of their pentavalent counterparts by several orders of magnitude. Non-methylating cells (urothelial cells and fibroblasts) seem to accumulate higher amounts of arsenic within the cell than the methylating hepatocytes. Cellular uptake and extrusion seem to be faster in hepatocytes than in urothelial cells. The correlation of uptake with toxicity indicates a significant role of membrane permeability towards toxicity. Furthermore, cytotoxic effects are more distinct in hepatocytes. Differential centrifugation studies revealed that elevated concentrations of arsenic are present in the ribosomal fraction of urothelial cells and in nucleic and mitochondrial fractions of hepatic cells. Further studies are needed to define the implications of the observed enrichment of arsenic in specific cellular organelles for its carcinogenic activity. This review summarizes our recent research on cellular uptake, distribution and toxicity of arsenic compounds in methylating and non-methylating cells.
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Affiliation(s)
- E Dopp
- Institute of Hygiene and Occupational Medicine, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany.
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Arsenic in drinking water and adult mortality: a population-based cohort study in rural Bangladesh. Epidemiology 2010; 20:824-30. [PMID: 19797964 DOI: 10.1097/ede.0b013e3181bb56ec] [Citation(s) in RCA: 127] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Arsenic is a potent human carcinogen and toxicant. Elevated concentration of arsenic in drinking water is a major public-health problem worldwide. We evaluated risks of adult mortality (due to cancer and cardiovascular and infectious diseases) in relation to arsenic exposure through drinking water. METHODS A cohort analysis was applied to survival data prospectively collected during 1991-2000 in a health and demographic surveillance system in Matlab, Bangladesh, where tubewells were installed beginning in the early 1970s. A total of 115,903 persons aged 15 or more years on 1 January 1991 were available for analysis. In this period, 9015 people died and 22,488 were lost to follow-up. Arsenic exposure data were derived from a survey in 2002-2003 of past and current water use and arsenic concentrations in all tubewells. We estimated risk of excess mortality in relation to arsenic exposure, using proportional hazards models. RESULTS Even at low levels (10-49 mug/L) of arsenic in drinking water, we observed increased risk of death due to all nonaccidental causes (hazard ratio = 1.16 [95% confidence interval = 1.06-1.26]). Increased risks at exposure of 50-149 microg/L were observed for death due to cancers (1.44 [1.06-1.95]), cardiovascular disease (1.16 [0.96-1.40]), and infectious diseases (1.30 [1.13-1.49]). We observed clear dose-response relationships for each of these causes. CONCLUSIONS Arsenic exposure through drinking water has generated excess adult mortality after 20-30 years of exposure.
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The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology. J Gastroenterol 2009; 44 Suppl 19:96-101. [PMID: 19148801 DOI: 10.1007/s00535-008-2258-6] [Citation(s) in RCA: 154] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2008] [Accepted: 07/10/2008] [Indexed: 02/07/2023]
Abstract
The epidemiology of hepatocellular cancer (HCC) can be viewed from several important perspectives. The conventional perspective includes the overall public health impact of HCC, which is increasing in incidence in many regions of the world. The epidemiology of HCC can also be viewed from the perspective of variation in underlying disease associations such as viral hepatitis or the recently recognized link to nonalcoholic fatty liver disease (NAFLD). Of perhaps increasing importance with recent advances in therapy of HCC, the epidemiology of HCC can also be viewed from the perspective of variation in HCC biology. This lesser known perspective may depend in part on the underlying liver disease and the cell origin of the cancer, whether of hepatocyte or stem cell origin. This aspect is likely to become central to diagnosis and management of HCC with the further development of targeted therapeutics. The relative efficacy of these agents will likely depend on the biochemical pathways active in a given hepatocellular malignancy. This, in turn, is likely to be related to the epidemiological associations of HCC.
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Well water arsenic exposure, arsenic induced skin-lesions and self-reported morbidity in Inner Mongolia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2009; 6:1010-25. [PMID: 19440430 PMCID: PMC2672384 DOI: 10.3390/ijerph6031010] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2009] [Accepted: 02/26/2009] [Indexed: 11/26/2022]
Abstract
Residents of the Bayingnormen region of Inner Mongolia have been exposed to arsenic-contaminated well water for over 20 years, but relatively few studies have investigated health effects in this region. We surveyed one village to document exposure to arsenic and assess the prevalence of arsenic-associated skin lesions and self-reported morbidity. Five-percent (632) of the 12,334 residents surveyed had skin lesions characteristics of arsenic exposure. Skin lesions were strongly associated with well water arsenic and there was an elevated prevalence among residents with water arsenic exposures as low as 5 μg/L-10 μg/L. The presence of skin lesions was also associated with self-reported cardiovascular disease.
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Liaw J, Marshall G, Yuan Y, Ferreccio C, Steinmaus C, Smith AH. Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile. Cancer Epidemiol Biomarkers Prev 2008; 17:1982-7. [PMID: 18708388 DOI: 10.1158/1055-9965.epi-07-2816] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Arsenic in drinking water is an established cause of lung, bladder, and skin cancers in adults and may also cause adult kidney and liver cancers. Some evidence for these effects originated from region II of Chile, which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water. In this article, we compare cancer mortality rates under the age of 20 in region II during 1950 to 2000 with those of unexposed region V, dividing subjects into those born before, during, or after the peak exposure period. Mortality from the most common childhood cancers, leukemia and brain cancer, was not increased in the exposed population. However, we found that childhood liver cancer mortality occurred at higher rates than expected. For those exposed as young children, liver cancer mortality between ages 0 and 19 was especially high: the relative risk (RR) for males born during this period was 8.9 [95% confidence interval (95% CI), 1.7-45.8; P = 0.009]; for females, the corresponding RR was 14.1 (95% CI, 1.6-126; P = 0.018); and for males and females pooled, the RR was 10.6 (95% CI, 2.9-39.2; P < 0.001). These findings suggest that exposure to arsenic in drinking water during early childhood may result in an increase in childhood liver cancer mortality.
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Affiliation(s)
- Jane Liaw
- Arsenic Health Effects Research Program, School of Public Health, University of California, 140 Warren Hall, Berkeley, CA 94720-7360, USA
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Wu JP, Chang LW, Yao HT, Chang H, Tsai HT, Tsai MH, Yeh TK, Lin P. Involvement of Oxidative Stress and Activation of Aryl Hydrocarbon Receptor in Elevation of CYP1A1 Expression and Activity in Lung Cells and Tissues by Arsenic: An In Vitro and In Vivo Study. Toxicol Sci 2008; 107:385-93. [DOI: 10.1093/toxsci/kfn239] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Liu J, Waalkes MP. Liver is a target of arsenic carcinogenesis. Toxicol Sci 2008; 105:24-32. [PMID: 18566022 PMCID: PMC2734307 DOI: 10.1093/toxsci/kfn120] [Citation(s) in RCA: 208] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2008] [Accepted: 06/11/2008] [Indexed: 12/11/2022] Open
Abstract
Inorganic arsenic is clearly a human carcinogen causing tumors of the skin, lung, urinary bladder, and possibly liver (IARC, 2004). At the time of construction of this monograph, the evidence for arsenic as a hepatocarcinogen in humans was considered controversial and in rodents considered insufficient. However, recent data has accumulated indicating hepatocarcinogenicity of arsenic. This forum reevaluates epidemiology studies, rodent studies together with in vitro models, and focuses on the liver as a target organ of arsenic toxicity and carcinogenesis. Hepatocellular carcinoma and hepatic angiosarcoma, have been frequently associated with environmental or medicinal exposure to arsenicals. Preneoplastic lesions, including hepatomegaly, hepatoportal sclerosis, fibrosis, and cirrhosis often occur after chronic arsenic exposure. Recent work in mice clearly shows that exposure to inorganic arsenic during gestation induces tumors, including hepatocellular adenoma and carcinoma, in offspring when they reach adulthood. In rats, the methylated arsenicals, dimethylarsinic acid promotes diethylnitrosamine-initiated liver tumors, whereas trimethylarsine oxide induces liver adenomas. Chronic exposure of rat liver epithelial cells to low concentrations of inorganic arsenic induces malignant transformation, producing aggressive, undifferentiated epithelial tumors when inoculated into the Nude mice. There are a variety of potential mechanisms for arsenical-induced hepatocarcinogenesis, such as oxidative DNA damage, impaired DNA damage repair, acquired apoptotic tolerance, hyperproliferation, altered DNA methylation, and aberrant estrogen signaling. Some of these mechanisms may be liver specific/selective. Overall, accumulating evidence clearly indicates that the liver could be an important target of arsenic carcinogenesis.
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Affiliation(s)
| | - Michael P. Waalkes
- Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Research Triangle Park, North Carolina
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Qin XJ, Hudson LG, Liu W, Ding W, Cooper KL, Liu KJ. Dual actions involved in arsenite-induced oxidative DNA damage. Chem Res Toxicol 2008; 21:1806-13. [PMID: 18707137 PMCID: PMC3606021 DOI: 10.1021/tx8001548] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Arsenic is a recognized human carcinogen, but the mechanism of carcinogenesis is not well understood. Oxidative stress and inhibition of DNA damage repair have been postulated as potential carcinogenic actions of arsenic. The present study tests the hypothesis that arsenite not only induces oxidative stress but also inhibits the activity of the DNA base excision repair protein, poly(ADP-ribose) polymerase-1 (PARP-1), leading to exacerbation of the oxidative DNA damage induced by arsenic. HaCat cells were treated with arsenite for 24 h before measuring 8-hydroxyl-2'-deoxyguanosine (8-OHdG), PARP-1 activity, and reactive oxygen species (ROS). Zinc supplementation and PARP-1 siRNA were used to increase or decrease, respectively, the PARP-1 protein's physiological function. At high concentrations (10 microM or higher), arsenite greatly induced oxidative DNA damage, as indicated by 8-OHdG formation. At lower concentrations (1 microM), arsenite did not produce detectable 8-OHdG, but was still able to effectively inhibit PARP-1 activity. Zinc supplementation reduced the formation of 8-OHdG, restored the PARP-1 activity inhibited by arsenite, but did not decrease ROS production. SiRNA knockdown of PARP-1 did not affect the 8-OHdG level induced by arsenic, while it greatly increased the 8-OHdG level produced by hydrogen peroxide indicating that PARP-1 is a molecular target of arsenite. Our findings demonstrate that in addition to inducing oxidative stress at higher concentrations, arsenite can also inhibit the function of a key DNA repair protein, PARP-1, even at very low concentrations, thus exacerbating the overall oxidative DNA damage produced by arsenite, and potentially, by other oxidants as well.
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Affiliation(s)
- Xu-Jun Qin
- Program of Toxicology, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, 87131, USA
- Department of Toxicology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, China
| | - Laurie G. Hudson
- Program of Toxicology, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, 87131, USA
| | - Wenlan Liu
- Program of Toxicology, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, 87131, USA
| | - Wei Ding
- Program of Toxicology, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, 87131, USA
| | - Karen L. Cooper
- Program of Toxicology, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, 87131, USA
| | - Ke Jian Liu
- Program of Toxicology, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, 87131, USA
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44
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Enhancements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism and carcinogenic risk via NNK/arsenic interaction. Toxicol Appl Pharmacol 2008; 227:108-14. [DOI: 10.1016/j.taap.2007.09.024] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2007] [Revised: 09/26/2007] [Accepted: 09/26/2007] [Indexed: 12/12/2022]
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Yang CY, Chang CC, Ho SC, Chiu HF. Is colon cancer mortality related to arsenic exposure? JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2008; 71:533-538. [PMID: 18338288 DOI: 10.1080/15287390801907509] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Arsenic has been well documented as the major risk factor for blackfoot disease (BFD), a unique peripheral vascular disease that was endemic to the southwestern coast of Taiwan, where residents consumed high-arsenic artesian well water for more than 50 yr. Chronic arsenic exposure was also reported to be associated with increased mortality attributed to colon cancer. A tap-water supply system was implemented in the early 1960s in the BFD-endemic areas. Artesian well water was no longer used for drinking and cooking after the mid-1970s. The objective of this study was to determine whether colon cancer mortality decreased after the improvement of the drinking-water supply system through elimination of arsenic ingestion from artesian well water. Standardized mortality ratios (SMRs) for colon cancer were calculated for the BFD-endemic area for the years 1971-2006. Results showed that mortality due to colon cancer declined in males, but not in females, gradually after the improvement of drinking-water supply system. Based on the reversibility criterion, the association between arsenic exposure and colon cancer incidence is likely to be causal for males but not females. The possibility that our results may be due to chance should be considered; however, gender-specific differences in arsenic metabolism may be a critical factor.
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Affiliation(s)
- Chun-Yuh Yang
- Faculty of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan 80708.
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46
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Yang CY, Chang CC, Chiu HF. Does arsenic exposure increase the risk for prostate cancer? JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2008; 71:1559-1563. [PMID: 18923998 DOI: 10.1080/15287390802392065] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Arsenic has been well documented as the major risk factor for blackfoot disease (BFD), a unique peripheral vascular disease that was endemic to the southwestern coast of Taiwan, where residents consumed artesian well water containing high levels of arsenic for more than 50 yr. Chronic arsenic exposure was also reported to be associated with mortality attributed to prostate cancer in a dose-response relationship. A tap-water supply system was implemented in the early 1960s in the BFD-endemic areas in Taiwan. Artesian well water was no longer used for drinking and cooking after the mid-1970s. The objective of this study was to determine whether prostate cancer mortality decreased after the improvement of drinking-water supply system through elimination of arsenic ingestion from artesian well water. Standardized mortality ratios (SMRs) for prostate cancer were calculated for the BFD-endemic area for the years 1971-2006. Results showed that mortality attributed to prostate cancer declined gradually after the improvement of drinking-water supply system. Based on the reversibility criterion, the association between arsenic exposure and development of prostate cancer is likely to be causal.
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Affiliation(s)
- Chun-Yuh Yang
- Faculty of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
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47
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Chiu HF, Lin MC, Yang CY. Primary intracerebral hemorrhage mortality reduction after installation of a tap-water supply system in an arseniasis-endemic area in southwestern Taiwan. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2007; 70:539-46. [PMID: 17365607 DOI: 10.1080/15287390600870940] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
Mortality and morbidity of vascular diseases, including stroke, are known to be associated with chronic exposure to inorganic arsenic through drinking water. A tap-water supply system was implemented in the early 1960s in the blackfoot disease (BFD) endemic areas of Taiwan. The objective of this study was to examine whether mortality attributed to stroke decreased among residents living in the BFD-endemic areas after the curtailment of arsenic exposure. Further it was of interest to determine whether arsenic exposure was related to a specific type of stroke. Standardized mortality ratios (SMRs) for stroke were calculated for the BFD endemic area for the years 1971-2000. The study results show that mortality due to primary intracerebral hemorrhage (PIH) declined gradually after the improvement of drinking-water supply system by elimination of arsenic exposure through removal of artesian well water. Based on the reversibility and specificity criteria, the association between arsenic exposure and mortality due to PIH is likely to be causal.
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Affiliation(s)
- Hui-Fen Chiu
- Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, Taiwan
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48
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Yang CY. Does arsenic exposure increase the risk of development of peripheral vascular diseases in humans? JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2006; 69:1797-804. [PMID: 16905509 DOI: 10.1080/15287390600630237] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Arsenic has been well documented as a major risk factor in the development of blackfoot disease (BFD), a unique peripheral vascular disease (PVD) endemic to the southwestern coast of Taiwan, where residents imbibed artesian well water containing excessive amounts of arsenic for more than 50 yr. Long-term arsenic exposure was also reported to be associated with mortality attributed to PVD. A tap-water supply system was implemented in the early 1960s in the BFD endemic areas. Artesian well water was no longer used for drinking and cooking after the mid-1970s. The objective of this study was to examine whether mortality attributed to PVD decreased after the consumption of artesian well water containing high concentrations of arsenic ceased and, if so, when the reduction occurred. Standardized mortality ratios (SMRs) for PVD were calculated for the BFD endemic area for the years 1971-2003. Cumulative-sum techniques were used to detect the occurrence of changes in the SMRs. Data showed that mortality due to PVD declined gradually for approximately 25 to 27 yr following cessation of consumption of this arsenic artesian well water. Based on the reversibility criterion, the association between arsenic exposure and PVD-attributed mortality is likely to be causal.
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Affiliation(s)
- Chun-Yuh Yang
- Institute of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung City, Taiwan.
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49
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Tapio S, Grosche B. Arsenic in the aetiology of cancer. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2006; 612:215-246. [PMID: 16574468 DOI: 10.1016/j.mrrev.2006.02.001] [Citation(s) in RCA: 195] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2005] [Revised: 01/25/2006] [Accepted: 02/07/2006] [Indexed: 12/28/2022]
Abstract
Arsenic, one of the most significant hazards in the environment affecting millions of people around the world, is associated with several diseases including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater contamination by arsenic is the main route of exposure. Inhalation of airborne arsenic or arsenic-contaminated dust is a common health problem in many ore mines. This review deals with the questions raised in the epidemiological studies such as the dose-response relationship, putative confounders and synergistic effects, and methods evaluating arsenic exposure. Furthermore, it describes the metabolic pathways of arsenic, and its biological modes of action. The role of arsenic in the development of cancer is elucidated in the context of combined epidemiological and biological studies. However, further analyses by means of molecular epidemiology are needed to improve the understanding of cancer aetiology induced by arsenic.
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Affiliation(s)
- Soile Tapio
- Federal Office for Radiation Protection, Department of Radiation Protection and Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
| | - Bernd Grosche
- Federal Office for Radiation Protection, Department of Radiation Protection and Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
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50
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Liu J, Xie Y, Ducharme DMK, Shen J, Diwan BA, Merrick BA, Grissom SF, Tucker CJ, Paules RS, Tennant R, Waalkes MP. Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure. ENVIRONMENTAL HEALTH PERSPECTIVES 2006; 114:404-11. [PMID: 16507464 PMCID: PMC1392235 DOI: 10.1289/ehp.8534] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p < 0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis of selected genes/proteins showed > 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis.
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Affiliation(s)
- Jie Liu
- Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
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