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Calderon-Segura ME, Ramírez-Guzmán A, Talavera-Mendoza O, Carbajal-López Y, Martínez-Valenzuela MDC, Mora-Herrera ME, Salinas-Alcántara L, Hurtado-Brito P. Genotoxic Biomonitoring in Children Living near the El Fraile Mine Tailings in Northern Guerrero State, Mexico. TOXICS 2022; 10:674. [PMID: 36355965 PMCID: PMC9694814 DOI: 10.3390/toxics10110674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/03/2022] [Accepted: 11/03/2022] [Indexed: 06/16/2023]
Abstract
A genotoxic study was conducted with 101 elementary school children (56 girls and 45 boys) in the 6-7, 8-9, and 10-12 age ranges from El Fraile rural community, which is located beside the El Fraile mine tailings in Taxco of Alarcon City, in northern Guerrero State, Mexico. For this, we used the alkaline comet assay in exfoliated buccal mucosa cells, scoring three genotoxic parameters: tail intensity, tail moment, and tail length. Additionally, we detected oxidative DNA damage through urinary 8-OHdG levels by enzyme-linked immunosorbent assay. We also evaluated a control group consisting of 101 children in the same age ranges from Chilpancingo City, Guerrero, who had never lived near mining zones. Genotoxic results showed that there was a significant increase in three genotoxic parameters and urinary 8-OHdG levels in the exposed children group compared with the control group. Analysis of MANOVA revealed that boys aged 8 and 9 years had higher DNA damage than girls from the same exposure group, and Spearman's analysis identified a positive correlation between DNA damage and sex and age. This study provides the first valuable genotoxic data in children living in areas with environmental pollution.
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Affiliation(s)
- María Elena Calderon-Segura
- Laboratorio de Toxicología Ambiental, Departamento de Ciencias Ambientales, Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán, Ciudad de México 04510, Mexico
| | - Alejandro Ramírez-Guzmán
- Escuela Superior de Ciencias de la Tierra, Universidad Autónoma de Guerrero, Ex Hacienda de San Juan Bautista s/n, Taxco el Viejo 40323, Mexico
| | - Oscar Talavera-Mendoza
- Escuela Superior de Ciencias de la Tierra, Universidad Autónoma de Guerrero, Ex Hacienda de San Juan Bautista s/n, Taxco el Viejo 40323, Mexico
| | - Yolanda Carbajal-López
- Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo de los Bravo 39087, Mexico
| | - María del Carmen Martínez-Valenzuela
- Instituto de Investigaciones en Ambiente y Salud, Universidad Autónoma de Occidente, Boulevar Macario Gaxiola, Carretera Internacional, Los Mochis 81200, Mexico
| | - Martha Elena Mora-Herrera
- Laboratorio de Fisiología y Biotecnología Vegetal, Centro Universitario Tenancingo, Universidad Autónoma, Tenancingo 52400, Mexico
| | - Liliana Salinas-Alcántara
- Laboratorio de Toxicología Ambiental, Departamento de Ciencias Ambientales, Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán, Ciudad de México 04510, Mexico
| | - Patricia Hurtado-Brito
- Laboratorio de Toxicología Ambiental, Departamento de Ciencias Ambientales, Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacán, Ciudad de México 04510, Mexico
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Abstract
Oxidative stress (OS) plays a key role in the pathophysiology of preterm infants. Accurate assessment of OS remains an analytical challenge that has been partially addressed during the last few decades. A plethora of approaches have been developed to assess preterm biofluids to demonstrate a link postnatally with preterm OS, giving rise to a set of widely employed biomarkers. However, the vast number of different analytic methods and lack of standardization hampers reliable comparison of OS-related biomarkers. In this chapter, we discuss approaches for the study of OS in prematurity with respect to methodologic considerations, the metabolic source of different biomarkers and their role in clinical studies.
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Wu CF, Hsiung CA, Tsai HJ, Cheng CM, Chen BH, Hu CW, Huang YL, Wu MT. Decreased levels of urinary di-2-ethylhexyl phthalate (DEHP) metabolites and biomarkers of oxidative stress in children exposed to DEHP-tainted foods in Taiwan in 2011: A 44-month follow-up. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2020; 266:115204. [PMID: 32745991 DOI: 10.1016/j.envpol.2020.115204] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 06/05/2020] [Accepted: 07/06/2020] [Indexed: 05/20/2023]
Abstract
A major health scandal involving DEHP-tainted (di-2-ethylhexyl phthalate) foodstuffs occurred in Taiwan in 2011. We investigated temporal relationships between urinary DEHP metabolites and biomarkers of oxidative stress in two cohorts of potentially affected children during that food scandal. One cohort was collected from Kaohsiung Medical University Hospital in southern Taiwan between May and June of 2011 (the KMUH cohort). This cohort was followed up at 2, 6, and 44 months. The other cohort was collected from a nationwide health survey conducted by Taiwan's National Health Research Institutes (the NHRI cohort) for potentially affected people between August 2012 and January 2013. Both cohorts only included children 10 years old and younger who had provided enough urine for analysis of urinary DEHP oxidative metabolites and two markers of oxidative stress: 8-oxo-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The KMUH cohort had a simultaneous and significant decrease in urinary DEHP metabolites, 8-OHdG, and MDA, with the lowest concentrations found at the 6-month follow up and maintained until the 44-month follow up, consistent with those from NHRI cohort at ∼15-18 months post-scandal (p > 0.05). There were decreases in both DEHP metabolites and oxidative stress markers across the populations, but no association was observed between DEHP metabolites and oxidative stress markers in individuals in the two cohorts. Continued follow-up is needed to determine long-term health consequences in these children.
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Affiliation(s)
- Chia-Fang Wu
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chao A Hsiung
- Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, Miaoli, Taiwan.
| | - Hui-Ju Tsai
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Ching-Mei Cheng
- Department of Laboratory Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
| | - Bai-Hsiun Chen
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chiung-Wen Hu
- Department of Public Health, Chung Shun Medical University, Taichung, Taiwan.
| | - Yeou-Lih Huang
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Ming-Tsang Wu
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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van der Schoor LWE, van Faassen MHJR, Kema I, Baptist DH, Olthuis AJ, Jonker JW, Verkade HJ, Groen H, Hulzebos CV. Blue LED phototherapy in preterm infants: effects on an oxidative marker of DNA damage. Arch Dis Child Fetal Neonatal Ed 2020; 105:628-633. [PMID: 32269147 DOI: 10.1136/archdischild-2019-317024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/08/2020] [Accepted: 03/11/2020] [Indexed: 01/26/2023]
Abstract
BACKGROUND Phototherapy is used on the majority of preterm infants with unconjugated hyperbilirubinaemia. The use of fluorescent tube phototherapy is known to induce oxidative DNA damage in infants and has largely been replaced by blue light-emitting diode phototherapy (BLP). To date, it is unknown whether BLP also induces oxidative DNA damage in preterm infants. OBJECTIVE To determine whether BLP in preterm infants induces oxidative DNA damage as indicated by 8-hydroxy-2'deoxyguanosine (8-OHdG). DESIGN Observational cohort study. METHODS Urine samples (n=481) were collected in a cohort of 40 preterm infants (24-32 weeks' gestational age) during the first week after birth. Urine was analysed for the oxidative marker of DNA damage 8-OHdG and for creatinine, and the 8-OHdG/creatinine ratio was calculated. Durations of phototherapy and levels of irradiance were monitored as well as total serum bilirubin concentrations. RESULTS BLP did not alter urinary 8-OHdG/creatinine ratios (B=0.2, 95% CI -6.2 to 6.6) at either low (10-30 µW/cm2/nm) or high (>30 µW/cm2/nm) irradiance: (B=2.3, 95% CI -5.7 to 10.2 and B=-3.0, 95% CI -11.7 to 5.6, respectively). Also, the 8-OHdG/creatinine ratios were independent on phototherapy duration (B=-0.1, 95% CI -0.3 to 0.1). CONCLUSIONS BLP at irradiances up to 35 µW/cm2/nm given to preterm infants ≤32 weeks' gestation does not affect 8-OHdG, an oxidative marker of DNA damage.
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Affiliation(s)
- Lori W E van der Schoor
- Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Ido Kema
- Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands
| | - Dyvonne H Baptist
- Department of Neonatology, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, The Netherlands
| | - Annelies J Olthuis
- Department of Neonatology, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, The Netherlands
| | - Johan W Jonker
- Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands
| | - Henkjan J Verkade
- Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands
| | - Henk Groen
- Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands
| | - Christian V Hulzebos
- Department of Neonatology, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, The Netherlands
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Morimoto M, Hashimoto T, Tsuda Y, Nakatsu T, Kitaoka T, Kyotani S. Assessment of oxidative stress in autism spectrum disorder using reactive oxygen metabolites and biological antioxidant potential. PLoS One 2020; 15:e0233550. [PMID: 32442231 PMCID: PMC7244111 DOI: 10.1371/journal.pone.0233550] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 05/07/2020] [Indexed: 12/27/2022] Open
Abstract
There are several studies on oxidative stress of Autism Spectrum Disorder (ASD), but in these cases there is no study to measure oxidative stress and antioxidant capacity at the same time or studies considering childhood development. Therefore, this study comprehensively assessed the level of oxidative stress in ASD children by simultaneously measuring reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The subjects were Japanese, 77 typical development (TD) children, 98 ASD children, samples were plasma. The subjects were divided into age groups: toddlers/preschool age (2–6 years) and school age (7–15 years), to compare the relationships among the d-ROMs levels and BAP/d-ROMs ratios. Furthermore, the correlations between the Parent-interview ASD Rating Scales (PARS) scores and the measured values were analyzed. The levels of d-ROMs were significantly higher in the ASD (7–15 years) than in TD (7–15 years). The PARS scores were significantly higher in the ASD and were significantly correlated with d-ROMs levels. These results suggested that d-ROMs and BAP/d-ROMs ratios could be objective, measured indicators that could be used in clinical practice to assess stress in ASD children.
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Affiliation(s)
- Masahito Morimoto
- Department of pharmacy, Japanese Red Cross Tokushima Hinomine Rehabilitation Center for People with Disabilities, Tokushima, Japan
- * E-mail:
| | - Toshiaki Hashimoto
- Department of pediatrics, Japanese Red Cross Tokushima Hinomine Rehabilitation Center for People with Disabilities, Tokushima, Japan
| | - Yoshimi Tsuda
- Department of pediatrics, Japanese Red Cross Tokushima Hinomine Rehabilitation Center for People with Disabilities, Tokushima, Japan
| | - Tadanori Nakatsu
- Department of pediatrics, Japanese Red Cross Tokushima Hinomine Rehabilitation Center for People with Disabilities, Tokushima, Japan
| | - Taisuke Kitaoka
- Graduate School of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan
| | - Shojiro Kyotani
- Graduate School of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan
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Calatayud M, Farias SS, de Paredes GS, Olivera M, Carreras NÁ, Giménez MC, Devesa V, Vélez D. Arsenic exposure of child populations in Northern Argentina. THE SCIENCE OF THE TOTAL ENVIRONMENT 2019; 669:1-6. [PMID: 30877956 DOI: 10.1016/j.scitotenv.2019.02.415] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 02/04/2019] [Accepted: 02/26/2019] [Indexed: 06/09/2023]
Abstract
Chronic exposure to inorganic arsenic (As) is associated with numerous adverse effects. Argentina is one of the countries affected by arsenicism; however, there are few studies that evaluate inorganic As exposure and its effects on child population. The aim of this study is to evaluate exposure to As through water and food in child populations living in the provinces of Santiago del Estero and Chaco (n = 101), and to determine the impact of this exposure analysing biomarkers of exposure (urine and hair As contents) and effect [8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG)]. The populations selected live in three areas with different levels of As in the drinking water (Santa Teresa de Carballo, 0.925 mg/L; Taco Pozo, 0.210 mg/L; Jumi Pozo, 0.016 mg/L). The As intakes through water and food are especially high in the areas with the greatest As exposure (Santa Teresa de Carballo, 1575 ± 8 μg/day; Taco Pozo, 386 ± 8 μg/day; Jumi Pozo, 39 ± 1 μg/day). The total As contents in most of the samples of hair (0.11-13.11 mg/kg) and urine (31-4258 μg/g creatinine) are higher than the reference values (hair: 1 mg/kg; urine: 50 μg/g creatinine). The increase in the level of As exposure alters the profile of metabolites in urine, with a decrease of dimethylarsinic acid (10%) and an increase in the percentages of monomethylarsonic acid (4%) and inorganic As (6%). The results also show high values of 8-OHdG (3.7-37.8 μg/g creatinine), a oxidative DNA damage marker, in the two areas with greater As exposure.
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Affiliation(s)
- Marta Calatayud
- Instituto de Agroquímica y Tecnología de Alimentos (CSIC), C/ Agustín Escardino 7, 46980 Paterna, Valencia, Spain
| | - Silvia Sara Farias
- Investigador Consulto Gerencia Química, Gerencia de Área de Seguridad y Ambiente, Comisión Nacional de Energía Atómica, Buenos Aires, Argentina
| | | | - Mónica Olivera
- Cátedra de Toxicología y Química Legal, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina
| | | | | | - Vicenta Devesa
- Instituto de Agroquímica y Tecnología de Alimentos (CSIC), C/ Agustín Escardino 7, 46980 Paterna, Valencia, Spain
| | - Dinoraz Vélez
- Instituto de Agroquímica y Tecnología de Alimentos (CSIC), C/ Agustín Escardino 7, 46980 Paterna, Valencia, Spain.
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Soto-Méndez MJ, Aguilera CM, Mesa MD, Campaña-Martín L, Martín-Laguna V, Solomons NW, Schümann K, Gil Á. Strong Associations Exist among Oxidative Stress and Antioxidant Biomarkers in the Circulating, Cellular and Urinary Anatomical Compartments in Guatemalan Children from the Western Highlands. PLoS One 2016; 11:e0146921. [PMID: 26790155 PMCID: PMC4720422 DOI: 10.1371/journal.pone.0146921] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 12/23/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND A series of antioxidant enzymes and non-enzymatic compounds act to protect cells from uncontrolled propagation of free radicals. It is poorly understood, though, to what extent and how their interaction is harmonized. OBJECTIVES To explore associative interactions among a battery of urinary and blood biomarkers of oxidative stress and enzymatic and non-enzymatic markers of the antioxidant defense system in children from low income households. METHODS For this cross-sectional descriptive study, urine, red cells, and plasma were sampled in 82 preschool children attending three daycare centers in Quetzaltenango Guatemala. The urinary oxidative stress biomarkers studied were F2-isoprostanes and 8-hydroxy-deoxy-guanosine. Red cell enzyme activities measured were: catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Circulating non-enzymatic antioxidants selected were: retinol, tocopherols, β-carotene and coenzymes Q9 and Q10. RESULTS In a Spearman rank-order correlation hemi-matrix, of 55 paired combinations of the 11 biomarkers, 28 (51%) were significantly correlated among each other (p ≤ 0.05), with the strongest association being retinol and tocopherols (r = 0.697, p<0.001), and 4 associations (9%) showed a trend (p> 0.5 to ≤ 0.10). F2-isoprostanes showed the greatest number of cross-associations, having significant interactions with 8 of the 10 remaining biomarkers. Goodness-of-fit modeling improved or maintained the r value for 24 of the significant interactions and for one of the 5 borderline associations. Multiple regression backward stepwise analysis indicated that plasma retinol, β-carotene and coenzyme Q10 were independent predictors of urinary F2-isoprostanes. CONCLUSION Numerous significant associations resulted among biomarkers of oxidation and responders to oxidation. Interesting findings were the apparent patterns of harmonious interactions among the elements of the oxidation-antioxidation systems in this population.
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Affiliation(s)
- María J. Soto-Méndez
- Center for the Studies of Sensory Impairment, Aging, and Metabolism–CeSSIAM–Guatemala City, Guatemala
- * E-mail:
| | - Concepción M. Aguilera
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology “José Mataix”, Center for Biomedical Research, University of Granada, Granada, Spain
- Networking Biomedical Research for Obesity and Nutrition–CIBERobn-, Madrid, Spain
| | - María D. Mesa
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology “José Mataix”, Center for Biomedical Research, University of Granada, Granada, Spain
- Thematic Networks of Cooperative Research–RETIC–, Carlos III Health Institute–ISCIII–, General Sub-Directorate for Research Assessment and Promotion and the European Regional Development Fund–ERDF–ref. RD12/0026, Madrid, Spain
| | - Laura Campaña-Martín
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology “José Mataix”, Center for Biomedical Research, University of Granada, Granada, Spain
| | - Victoria Martín-Laguna
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology “José Mataix”, Center for Biomedical Research, University of Granada, Granada, Spain
| | - Noel W. Solomons
- Center for the Studies of Sensory Impairment, Aging, and Metabolism–CeSSIAM–Guatemala City, Guatemala
| | - Klaus Schümann
- Molecular Nutrition Unit, ZIEL, Research Center for Nutrition and Food Science, Technische Universität München, Freising, Germany
| | - Ángel Gil
- Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology “José Mataix”, Center for Biomedical Research, University of Granada, Granada, Spain
- Networking Biomedical Research for Obesity and Nutrition–CIBERobn-, Madrid, Spain
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Lin W, Zhu T, Xue T, Peng W, Brunekreef B, Gehring U, Huang W, Hu M, Zhang Y, Tang X. Association between changes in exposure to air pollution and biomarkers of oxidative stress in children before and during the Beijing Olympics. Am J Epidemiol 2015; 181:575-83. [PMID: 25770981 DOI: 10.1093/aje/kwu327] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Accepted: 10/23/2014] [Indexed: 11/14/2022] Open
Abstract
It is not known whether exposure to air pollutants causes systemic oxidative stress in children. We investigated the association between exposure to air pollution and biomarkers of oxidative stress in relation to a governmental air quality intervention implemented during the 2008 Beijing Olympic Games. We studied 36 schoolchildren during 5 time periods before and during the Olympic Games in Beijing (June 2007-September 2008). The oxidative stress biomarkers 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and malondialdehyde were measured in urine samples collected daily during each period. Generalized estimating equations were used to examine the relationship between repeated biomarker measurements and ambient air pollutant levels. During the Olympic intervention period, substantial reductions in air pollution (-19% to -72%), urinary 8-oxodG concentrations (-37.4%; 95% confidence interval: -53.5, -15.7), and urinary malondialdehyde concentrations (-25.3%; 95% confidence interval: -34.3, -15.1) were found. Malondialdehyde and 8-oxodG were significantly associated with concentrations of black carbon, fine particulate matter with an aerodynamic with diameter less than 2.5 μm, sulfur dioxide, nitrogen dioxide, and carbon monoxide. Biomarker changes per each interquartile-range increase in pollutants were largest at lag 0 or lag 1. In a 2-pollutant model, the most robust associations were for black carbon. These findings suggest that exposure to black carbon leads to systemic oxidative stress in children.
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Kato E, Ibara S, Kumazawa K, Maruyama Y, Tokuhisa T, Matsui T, Shimono R, Maede Y, Minakami H. Effects of supplemental oxygen on urinary 8-hydroxy-2'-deoxyguanosine levels in extremely low birth weight infants. Free Radic Res 2014; 48:1285-90. [PMID: 25096515 DOI: 10.3109/10715762.2014.951841] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 ± 6.9 vs. 5.6 ± 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.
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Affiliation(s)
- E Kato
- Division of Neonatology, Perinatal Medical Center, Kagoshima City Hospital , Kagoshima , Japan
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Harper KN, Liu X, Hall MN, Ilievski V, Oka J, Calancie L, Slavkovich V, Levy D, Siddique A, Alam S, Mey JL, van Geen A, Graziano JH, Gamble MV. A dose-response study of arsenic exposure and markers of oxidative damage in Bangladesh. J Occup Environ Med 2014; 56:652-8. [PMID: 24854259 PMCID: PMC4050339 DOI: 10.1097/jom.0000000000000166] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To evaluate the dose-response relationship between arsenic (As) exposure and markers of oxidative damage in Bangladeshi adults. METHODS We recruited 378 participants drinking water from wells assigned to five water As exposure categories; the distribution of subjects was as follows: (1) less than 10 μg/L (n=76); (2) 10 to 100 μg/L (n=104); (3) 101 to 200 μg/L (n=86); (4) 201 to 300 μg/L (n=67); and (5) more than 300 μg/L (n=45). Arsenic concentrations were measured in well water, as well as in urine and blood. Urinary 8-oxo-2'-deoxyguanosine and plasma protein carbonyls were measured to assess oxidative damage. RESULTS None of our measures of As exposure were significantly associated with protein carbonyl or 8-oxo-2'-deoxyguanosine levels. CONCLUSIONS We found no evidence to support a significant relationship between long-term exposure to As-contaminated drinking water and biomarkers of oxidative damage among Bangladeshi adults.
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Affiliation(s)
- Kristin N. Harper
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Xinhua Liu
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Megan N. Hall
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Vesna Ilievski
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Julie Oka
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Larissa Calancie
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Vesna Slavkovich
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Diane Levy
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Abu Siddique
- Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh
| | - Shafiul Alam
- Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh
| | - Jacob L. Mey
- Lamont-Doherty Earth Observatory, Columbia University, Palisades, NY 10964
- Kingsbridge Community College, New York, NY 11235
| | - Alexander van Geen
- Lamont-Doherty Earth Observatory, Columbia University, Palisades, NY 10964
| | - Joseph H. Graziano
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
| | - Mary V. Gamble
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032
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Kaneko K, Kimata T, Tsuji S, Ohashi A, Imai Y, Sudo H, Kitamura N. Measurement of urinary 8-oxo-7,8-dihydro-2-deoxyguanosine in a novel point-of-care testing device to assess oxidative stress in children. Clin Chim Acta 2012; 413:1822-6. [DOI: 10.1016/j.cca.2012.07.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2012] [Revised: 07/08/2012] [Accepted: 07/09/2012] [Indexed: 10/28/2022]
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12
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Mori T, Yoshinaga J, Suzuki K, Mizoi M, Adachi SI, Tao H, Nakazato T, Li YS, Kawai K, Kasai H. Exposure to polycyclic aromatic hydrocarbons, arsenic and environmental tobacco smoke, nutrient intake, and oxidative stress in Japanese preschool children. THE SCIENCE OF THE TOTAL ENVIRONMENT 2011; 409:2881-2887. [PMID: 21570106 DOI: 10.1016/j.scitotenv.2011.04.028] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2011] [Revised: 04/14/2011] [Accepted: 04/14/2011] [Indexed: 05/30/2023]
Abstract
The association between oxidative stress and exposure to environmental chemicals was assessed in a group of Japanese preschool children. The concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 1-hydroxypyrene (1-OHP), inorganic arsenic (iAs) and monomethylarsonic acid (MMA), and cotinine in spot urine samples, collected from 134 children (3-6 yrs) from a kindergarten in Kanagawa, Japan, were measured as biomarkers of oxidative stress or exposure to environmental chemicals. For 76 subjects of the 134, intakes of anti-oxidant nutrients (vitamins A, C, and E, manganese, copper, zinc and selenium (Se)) were estimated from a food consumption survey carried out 2-4 weeks after urine sampling and by urine analysis (Se). The median (min-max) creatinine-corrected concentrations of urinary biomarkers were 4.45 (1.98-12.3), 0.127 (0.04-2.41), 4.78 (1.18-12.7), and 0.62 (<0.6-19.0) μg/g cre for 8-OHdG, 1-OHP, iAs+MMA, and cotinine, respectively. Multiple regression analysis was carried out using 8-OHdG concentration as a dependent variable and urinary biomarkers of exposure and Se intake, intakes of vitamins and biological attributes of the subjects as independent variables. To explain 8-OHdG concentrations, intake of vitamin A and age were significant variables with negative coefficients, while 1-OHP concentration had a positive coefficient. These results indicated that oxidative stress of children is affected by chemical exposure at environmental levels, by nutrient intake and by physiological factors in a complex manner. On the other hand, unstable statistical results due to sub-grouping of subject, based on the availability of food consumption data, were found: the present results should further be validated by future studies with suitable research design.
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Affiliation(s)
- Takuya Mori
- Department of Environmental Studies, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8563, Japan
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Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part II. Oxidative damage. Mutat Res 2009; 669:20-6. [PMID: 19433097 DOI: 10.1016/j.mrfmmm.2009.04.010] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2009] [Revised: 04/21/2009] [Accepted: 04/24/2009] [Indexed: 11/23/2022]
Abstract
Oxidative damage to macromolecules may have numerous negative health consequences. We measured oxidative damage to DNA, proteins and lipids in 80 newborns and 79 mothers, analyzed the effect of mother's tobacco smoke exposure on oxidative stress, and assessed correlations between oxidative stress markers and bulky and PAH (polycyclic aromatic hydrocarbons)-specific DNA adducts. Mean levels (+/-S.D.) of 8-oxodeoxyguanosine (8-oxodG) per 10(5) dG in the placenta were 2.85+/-0.78; we did not see a difference between 8-oxodG levels in newborns born to mothers exposed and unexposed to tobacco smoke. Protein carbonyl levels, a marker of protein oxidation, were comparable in the umbilical cord and in maternal venous blood plasma (17.4+/-3.2 and 17.6+/-4.2nmol/ml plasma in newborns and mothers, respectively, p=0.66). Lipid peroxidation measured as levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) in plasma was significantly higher in newborns than in mothers (362+/-129 and 252+/-130pg/ml in newborns and mothers, respectively, p<0.001). We did not find any effect of tobacco smoke exposure on either biomarker in any group. Levels of both protein carbonyls and 15-F(2t)-IsoP in cord blood significantly correlated with those in maternal plasma (p<0.001). 8-oxodG levels positively correlated with plasma carbonyls in cord plasma, as well as with cotinine levels (marker of tobacco smoke exposure) in maternal plasma. 8-oxodG levels also correlated with bulky DNA adducts in lymphocyte DNA of newborns and mothers and with PAH-DNA adducts in the placenta. Our results showed higher lipid peroxidation in newborns than in mothers, close correlation of analyzed oxidative stress markers between newborns and mothers, and a relationship between oxidative stress and induction of DNA adducts.
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Evans MD, Singh R, Mistry V, Sandhu K, Farmer PB, Cooke MS. Analysis of urinary 8-oxo-7,8-dihydro-purine-2'-deoxyribonucleosides by LC-MS/MS and improved ELISA. Free Radic Res 2008; 42:831-40. [PMID: 18985483 DOI: 10.1080/10715760802506323] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Non-invasive monitoring of oxidative stress is highly desirable. Urinary 7,8-8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a biologically relevant and convenient analytical target. However, immunoassays can over-estimate levels of urinary 8-oxodG. Measurement of more than one DNA oxidation product in urine would be advantageous in terms of mechanistic information. Urines samples were analysed for 8-oxodG by solid-phase extraction/LC-MS/MS and ELISA. The solid-phase extraction/LC-MS/MS assay was also applied to the analysis of urinary 7,8-dihydro-8-oxo-2'-deoxyadenosine (8-oxodA). Concurring with previous reports, urinary 8-oxodG measured by ELISA was significantly higher than levels measured by LC-MS/MS. However, apparent improvement in the specificity of the commercially available Japanese Institute for the Control of Ageing (JaICA) ELISA brought mean LC-MS/MS and ELISA measurements of urinary 8-oxodG into agreement. Urinary 8-oxodA was undetectable in all urines, despite efficient recovery by solid phase extraction. Exploitation of the advantages of ELISA may be enhanced by a simple modification to the assay procedure, although chromatographic techniques still remain the 'gold standard' techniques for analysis of urinary 8-oxodG. Urinary 8-oxodA is either not present or below the limit of detection of the instrumentation.
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Affiliation(s)
- Mark D Evans
- Department of Cancer, Radiation and Oxidative Stress Section, Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester, Leicester, UK.
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15
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High susceptibility of neonatal mice to molecular, biochemical and cytogenetic alterations induced by environmental cigarette smoke and light. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2008; 659:137-46. [DOI: 10.1016/j.mrrev.2007.11.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2007] [Revised: 10/25/2007] [Accepted: 11/01/2007] [Indexed: 11/21/2022]
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16
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Fukuda M, Yamauchi H, Yamamoto H, Aminaka M, Murakami H, Kamiyama N, Miyamoto Y, Koitabashi Y. The evaluation of oxidative DNA damage in children with brain damage using 8-hydroxydeoxyguanosine levels. Brain Dev 2008; 30:131-6. [PMID: 17766071 DOI: 10.1016/j.braindev.2007.07.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2006] [Revised: 05/21/2007] [Accepted: 07/12/2007] [Indexed: 10/22/2022]
Abstract
Urinary and cerebrospinal fluid (CSF) levels of 8-hydroxydeoxyguanosine (8-OHdG) were examined to estimate the relevance of oxidative stress in children with brain damage. Urinary 8-OHdG levels were measured in 51 children with various forms of central nervous system (CNS) disorders (status epilepticus [SE], hypoxic-ischemic encephalopathy [HIE], CNS infections and chronic epilepsy) and these levels were compared with those in 51 healthy children. CSF 8-OHdG levels were measured in 25 children with brain damage and in 19 control subjects. In addition, urinary and CSF levels of 8-OHdG were compared between the children with brain damage and healthy children. Finally, the relationship between urinary and CSF levels of 8-OHdG was determined in 12 children that provided both urinary and CSF samples. Our results showed that urinary 8-OHdG levels in children with HIE and CNS infections were higher than those of controls (Steel test; p < 0.05 and p < 0.05, respectively) and that CSF 8-OHdG levels were higher in children with SE, HIE, and CNS infections than in control subjects (Steel test; p < 0.01, 0.05 and 0.05, respectively). In addition, a positive correlation between the levels of urinary and CSF 8-OHdG was noted in the 12 children that provided both CSF and urinary samples (Spearman's rank correlation; rho = 0.82, p < 0.01). Further, we observed changes in the urinary 8-OHdG in a patient with HHV-6 encephalopathy, and found that the changes correlated well with the patient's clinical condition. These results suggest that oxidative stress is strongly related to acute brain damage in children, and that 8-OHdG is a useful marker of brain damage. Therefore, repeated measurements of urinary 8-OHdG may be helpful in estimating the extent of brain damage.
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Affiliation(s)
- Miho Fukuda
- Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.
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17
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Wong RH, Kuo CY, Hsu ML, Wang TY, Chang PI, Wu TH, Huang S. Increased levels of 8-hydroxy-2 -deoxyguanosine attributable to carcinogenic metal exposure among schoolchildren. ENVIRONMENTAL HEALTH PERSPECTIVES 2005; 113:1386-90. [PMID: 16203252 PMCID: PMC1281285 DOI: 10.1289/ehp.7401] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer. However, the health effects of arsenic, chromium, and nickel exposures are equivocal for children. Therefore, we performed a cross-sectional study to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress to DNA in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking children using atomic absorption spectrometry. As a biomarker for oxidative stress, urinary 8-hydroxy-2 -deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine. No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean +/- SE, 16.0 +/- 1.3; vs. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 +/- 1.6; vs. low arsenic/low chromium, p = 0.25), high arsenic/low chromium (12.9 +/- 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 +/- 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children.
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Affiliation(s)
- Ruey-Hong Wong
- Department of Public Health, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan
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Tondel M, Arynchyn A, Jönsson P, Persson B, Tagesson C. Urinary 8-hydroxydeoxyguanosine in Belarussian children relates to urban living rather than radiation dose after the chernobyl accident: a pilot study. ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2005; 48:515-9. [PMID: 15886892 DOI: 10.1007/s00244-004-0079-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2004] [Accepted: 11/16/2004] [Indexed: 05/02/2023]
Abstract
As a result of the Chernobyl accident in 1986, exposure to radioactive cesium is still a concern in the contaminated regions of Belarus. We tested the hypothesis that long-term radiation exposure from the Chernobyl accident might increase the urinary excretion of the oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), in Belarussian children. Urinary 8-OHdG was determined in two groups of children (-n = 31 and n = 46) -living in contaminated and uncontaminated areas of Belarus, respectively (the majority of the unexposed children lived in the capital Minsk). The children from the contaminated areas had a significantly higher annual summary effective dose but significantly lower urinary 8-OHdG levels than the children from the uncontaminated areas. Unexpectedly, children living in uncontaminated urban areas had significantly higher urinary 8-OHdG levels than children living in uncontaminated rural areas. There was no statistically significant effect of sex or body mass index on urinary 8-OHdG, but there was a weak significant inverse correlation to age as well as to the annual summary effective dose. These findings suggest that radiation from the Chernobyl accident is now a less important contributor to oxidative stress in Belarussian children than urban living.
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Affiliation(s)
- M Tondel
- Division of Occupational and Environmental Medicine, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Sweden.
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19
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Evans MD, Dizdaroglu M, Cooke MS. Oxidative DNA damage and disease: induction, repair and significance. MUTATION RESEARCH/REVIEWS IN MUTATION RESEARCH 2004; 567:1-61. [PMID: 15341901 DOI: 10.1016/j.mrrev.2003.11.001] [Citation(s) in RCA: 902] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2003] [Revised: 11/12/2003] [Accepted: 11/12/2003] [Indexed: 04/08/2023]
Abstract
The generation of reactive oxygen species may be both beneficial to cells, performing a function in inter- and intracellular signalling, and detrimental, modifying cellular biomolecules, accumulation of which has been associated with numerous diseases. Of the molecules subject to oxidative modification, DNA has received the greatest attention, with biomarkers of exposure and effect closest to validation. Despite nearly a quarter of a century of study, and a large number of base- and sugar-derived DNA lesions having been identified, the majority of studies have focussed upon the guanine modification, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-OH-dG). For the most part, the biological significance of other lesions has not, as yet, been investigated. In contrast, the description and characterisation of enzyme systems responsible for repairing oxidative DNA base damage is growing rapidly, being the subject of intense study. However, there remain notable gaps in our knowledge of which repair proteins remove which lesions, plus, as more lesions identified, new processes/substrates need to be determined. There are many reports describing elevated levels of oxidatively modified DNA lesions, in various biological matrices, in a plethora of diseases; however, for the majority of these the association could merely be coincidental, and more detailed studies are required. Nevertheless, even based simply upon reports of studies investigating the potential role of 8-OH-dG in disease, the weight of evidence strongly suggests a link between such damage and the pathogenesis of disease. However, exact roles remain to be elucidated.
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Affiliation(s)
- Mark D Evans
- Oxidative Stress Group, Department of Clinical Biochemistry, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, LE2 7LX, UK
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Shoji H, Shimizu T, Shinohara K, Oguchi S, Shiga S, Yamashiro Y. Suppressive effects of breast milk on oxidative DNA damage in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2004; 89:F136-8. [PMID: 14977897 PMCID: PMC1756038 DOI: 10.1136/adc.2002.018390] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND Human milk contains many kinds of antioxidant and is considered to prevent diseases mediated by oxygen free radicals in very low birthweight (VLBW) infants. AIMS To examine the antioxidant effects of breast milk in VLBW infants by determining urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion, which is known to be a non-invasive marker for in vivo oxidative DNA damage. METHODS Urinary 8-OHdG concentrations were measured in 15 breast fed and 14 formula fed VLBW infants at 2, 7, 14, and 28 days of age. RESULTS Urinary 8-OHdG excretion at 14 and 28 days of age was significantly lower than at 2 and 7 days of age in the breast fed group, and significantly lower than in the formula fed group. CONCLUSION This is the first direct evidence of the antioxidant action of human milk in VLBW infants.
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Affiliation(s)
- H Shoji
- Department of Paediatrics, Juntendo University School of Medicine, Tokyo, Japan
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21
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Peng T, Shen HM, Liu ZM, Yan LN, Peng MH, Li LQ, Liang RX, Wei ZL, Halliwell B, Ong CN. Oxidative DNA damage in peripheral leukocytes and its association with expression and polymorphisms of hOGG 1: A study of adolescents in a high risk region for hepatocellular carcinoma in China. World J Gastroenterol 2003; 9:2186-93. [PMID: 14562375 PMCID: PMC4656460 DOI: 10.3748/wjg.v9.i10.2186] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China.
METHODS: Peripheral leukocytes’ DNA 7,8-dihydro-8-oxoguanine (8-oxoG) and repair enzyme hOGG1 were quantified by flow-cytometry. hOGG1-Cys326Ser single nucleotide polymorphism (SNP) was distinguished by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) assay.
RESULTS: There was a positive correlation between 8-oxoG and repair enzyme hOGG1 expression (P < 0.001). HCC children (n = 21) in Fusui county had a higher level of hOGG1 (P < 0.01) and a lower level of 8-oxoG (P < 0.05) than the controls (n = 63) in Nanning city. Children in Nanning exposed to passive-smoking had a higher hOGG1 expression (P < 0.05) than the non-exposers. 8-oxoG and hOGG1 were negatively correlated with body mass index, while hOGG1 was positively correlated with age. There was a peak of 8-oxoG level nearby the 12 year point. Individuals with the hOGG1 326Ser allele had a significantly marginal higher concentration of leukocyte 8-oxoG level than hOGG1 326Cys allele.
CONCLUSION: This is the first report using flow-cytometry to simultaneously quantify both the DNA oxidative damage and its repairing enzyme hOGG1. The results provide new insights towards a better understanding of the mechanisms of oxidative stress in a population highly susceptible to hepatocarcinogenesis.
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Affiliation(s)
- Tao Peng
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
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Abstract
Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.
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Affiliation(s)
- Marcus S Cooke
- Oxidative Stress Group, Department of Clinical Biochemistry, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, LE2 7LX, UK.
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Abstract
Free radicals and other reactive species are generated in vivo and many of them can cause oxidative damage to DNA. Although there are methodological uncertainties about accurate quantitation of oxidative DNA damage, the levels of such damage that escape immediate repair and persist in DNA appear to be in the range that could contribute significantly to mutation rates in vivo. The observation that diets rich in fruits and vegetables can decrease both oxidative DNA damage and cancer incidence is consistent with this. By contrast, agents increasing oxidative DNA damage usually increase risk of cancer development. Such agents include cigarette smoke, several other carcinogens, and chronic inflammation. Rheumatoid arthritis and diabetes are accompanied by increased oxidative DNA damage but the pattern of increased cancer risk seems unusual. Other uncertainties are the location of oxidative DNA damage within the genome and the variation in rate and level of oxidative damage between different body tissues. In well-nourished human volunteers, fruits and vegetables have been shown to decrease oxidative DNA damage in several studies, but data from short-term human intervention studies suggest that the protective agents are not vitamin C, vitamin E, beta-carotene, or flavonoids.
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Affiliation(s)
- Barry Halliwell
- Department of Biochemistry, National University of Singapore, Singapore 119260.
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Abu-Qare A, Abou-Donia M. Increased 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage in rat urine following a single dermal dose of DEET (N, N-diethyl-m-toluamide), and permethrin, alone and in combination. Toxicol Lett 2000; 117:151-60. [PMID: 11087981 DOI: 10.1016/s0378-4274(00)00257-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Levels of the biomarker of DNA oxidative damage 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat urine following dermal exposure to DEET (N,N-diethyl-m-toluamide) and permethrin, alone and in combination have been determined. A group of five rats for each time point were treated with a single dermal dose of 400 mg/kg of DEET, 1.3 mg/kg of permethrin or their combination. Urine samples were collected 2,4,8,16,24,48, and 72 h following application. Control urine samples of rats treated with ethanol were also collected at the same time intervals. Solid phase extraction coupled with high performance liquid chromatography (HPLC) with UV detection at 254 nm was used for determination of 2'-deoxyguanosine, and (8-OHdG). The limits of detection (LOD) were 0.5 ng of both 2'-deoxyguanosine and 8-OHdG. Their average percentage recoveries from urine samples were between 70-85%. A single dermal dose of DEET or in combination with permethrin significantly induced levels of (8-OHdG) that are excreted in the urine over the time course of the study compared to control urine samples. Permethrin did not cause significant increase in the amount of 8-OHdG in the urine. Levels of 8-OHdG in urine excreted at 24 h were 1009+/-342, 1701+/-321, 1140+/-316, and 1897+/-231 ng following treatment with ethanol, DEET, permethrin, and DEET+permethrin, respectively. The results indicate that dermal administration of DEET could generate free radical species hence cause DNA oxidative damage in rats.
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Affiliation(s)
- A Abu-Qare
- Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
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Halliwell B. Why and how should we measure oxidative DNA damage in nutritional studies? How far have we come? Am J Clin Nutr 2000; 72:1082-7. [PMID: 11063432 DOI: 10.1093/ajcn/72.5.1082] [Citation(s) in RCA: 154] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Free radicals and other reactive species are constantly generated in vivo and cause oxidative damage to DNA at a rate that is probably a significant contributor to the age-related development of cancer. Agents that decrease oxidative DNA damage should thus decrease the risk of cancer development. That is, oxidative DNA damage is a "biomarker" for identifying persons at risk (for dietary or genetic reasons, or both) of developing cancer and for suggesting how the diets of these persons could be modified to decrease that risk. This biomarker concept presupposes that we can measure oxidative damage accurately in DNA from relevant tissues. Little information is available on whether oxidative DNA damage in blood cells mirrors such damage in tissues at risk of cancer development. Measurement of 8-hydroxylated guanine (eg, as 8-hydroxy-2'-deoxyguanosine; 8OHdG) is the commonest method of assessing DNA damage, but there is no consensus on what the true levels are in human DNA. If the lowest levels reported are correct, 8OHdG may be only a minor product of oxidative DNA damage. Indeed, 8OHdG may be difficult to measure because of the ease with which it is formed artifactually during isolation, hydrolysis, and analysis of DNA. Mass spectrometry can accurately measure a wide spectrum of DNA base damage products, but the development of liquid chromatography-mass spectrometry techniques and improved DNA hydrolysis procedures is urgently required. The available evidence suggests that in Western populations, intake of certain fruit and vegetables can decrease oxidative DNA damage, whereas ascorbate, vitamin E, and beta-carotene cannot.
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Affiliation(s)
- B Halliwell
- Department of Biochemistry, National University of Singapore.
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England T, Beatty E, Rehman A, Nourooz-Zadeh J, Pereira P, O'Reilly J, Wiseman H, Geissler C, Halliwell B. The steady-state levels of oxidative DNA damage and of lipid peroxidation (F2-isoprostanes) are not correlated in healthy human subjects. Free Radic Res 2000; 32:355-62. [PMID: 10741856 DOI: 10.1080/10715760000300351] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Oxidative damage to DNA in human tissues can be determined by measuring multiple products of oxidative damage to the purine and pyrimidine bases using gas chromatography-mass spectrometry (GC-MS). Oxidative damage to lipids (lipid peroxidation) can be quantitated by the mass spectrometry-based determination of F2-isoprostanes, specific end-products of the peroxidation of arachidonic acid residues in lipids. For both DNA base damage products and 8-epi prostaglandin F2alpha (PGF2alpha), there is a wide variation in levels between different healthy human subjects. We measured multiple products of oxidative damage to DNA bases in white cells, and 8-epi PGF2alpha in plasma, from blood samples obtained from healthy human subjects in the UK and in Portugal. No correlation of 8-epi PGF2alpha levels with levels of any modified DNA base (including 8-hydroxyguanine) was observed. We conclude that no single parameter can be measured as an index of "oxidative stress" or "oxidative damage" in vivo.
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Affiliation(s)
- T England
- International Antioxidant Research Centre, King's College, Guys Campus, London, UK
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27
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Halliwell B. Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 1999; 443:37-52. [PMID: 10415430 DOI: 10.1016/s1383-5742(99)00009-5] [Citation(s) in RCA: 228] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Humans are exposed to many carcinogens, but the most significant may be the reactive species derived from metabolism of oxygen and nitrogen. Nitric oxide seems unlikely to damage DNA directly, but nitrous acid produces deamination and peroxynitrite leads to both deamination and nitration. Scavenging of reactive nitrogen species generated in the stomach may be an important role of flavonoids, flavonoids and other plant-derived phenolic compounds. Different reactive oxygen species produce different patterns of damage to DNA bases, e.g., such patterns have been used to implicate hydroxyl radical as the ultimate agent in H(2)O(2)-induced DNA damage. Levels of steady-state DNA damage in vivo are consistent with the concept that such damage is a major contributor to the age-related development of cancer and so such damage can be used as a biomarker to study the effects of diet or dietary supplements on risk of cancer development, provided that reliable assays are available. Methodological questions addressed in this article include the validity of measuring 8-hydroxydeoxyguanosine (8OHdG) in cellular DNA or in urine as a biomarker of DNA damage, the extent of artifact formation during analysis of oxidative DNA damage by gas chromatography-mass spectrometry and the levels of oxidative damage in mitochondrial DNA.
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Affiliation(s)
- B Halliwell
- Department of Biochemistry, National University of Singapore, Kent Ridge Crescent, Singapore 119260, Singapore.
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