Original Articles
Copyright ©The Author(s) 1998. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 1998; 4(4): 307-310
Published online Aug 15, 1998. doi: 10.3748/wjg.v4.i4.307
Modification of ricin and its hepatotoxicity and activity against hepatocellular cancer in mice
Wen-Xue Wang, Ju-Ying Dong, Si-Yuan Zhou, Wen-Li Li, Ying Zhao
Wen-Xue Wang, Ju-Ying Dong, Si-Yuan Zhou, Wen-Li Li, Ying Zhao, Department of Toxicology, Faculty of Military Health Service and Statistics, Fourth Military Medical University, Xi’an 710033, Shaanxi Province, China
Wen-Xue Wang, male, was born on 1938-11-23 in Laoting County, Hebei Province, China and graduated from the Northwest University, now professor of toxicology, specializing in research of poisons, drugs and protein modification and activities, having 63 papers published.
Author contributions: All authors contributed equally to the work.
Correspondence to: Prof. Wen-Xue Wang, 403-2 Room, Fourth Military Medical University, Xi’an 710032, China
Telephone: +86-29-3221616-75676
Received: March 20, 1998
Revised: April 22, 1998
Accepted: May 14, 1998
Published online: August 15, 1998
Abstract

AIM: To observe the effects of ricin (RT) with and without chemicalmodification on both hepatotoxicity of mice and activity against hepatocellular cancer (HCC), and evaluate the possibility to improve RT anticancer activity via chemical modification.

METHODS: RT was modified with N-succinimidyl3 (2-pyridyldithio) propionate (SPDP), a heterobifunctional cross-linker, and SPDP derivative of RT (PDP-R) was obtained. The serum glutathione-s-transferase (SGST) activity, as an index of liver damage, was determined in mice intoxicated with RT and PDP-R, at various doses and time.The tissue damage of HCC in the nude mice ip injected with PDP-R was compared with that with RT at the same dose by immunohistochemical method, the relative content of both RT and PDP-R in the HCC tissues was measured by computerized image-analysis.

RESULTS: The SGST activities increased with doses or/and time intoxicated with both RT and PDP-R, and the increase in the value of RT group was more significant than that in the PDP-R group; the SGST activity of RT group was 2.8-fold (P < 0.01) of PDP-R group at a dose of 12.5 μg/kg for 42 h, showing the much lower toxicity of R-PDP than that of RT. Under an optical microscope, hemolysis and necrosis of massive cells in the HCC tissues of PDP-R group were observed and the ratio of necrosis mounted to 90.5% while the corresponding value of RT group only to 62.5%. With computerized image-analysis, the average relative content of RT and PDP-R in the HCC tissues, represented as greyness, was 140.06 ± 3.43 and 169.10 ± 2.74, respectively. There was significant difference between the two (P < 0.05), indicating the higher content of PDP-R in the HCC tissue than that of RT.

CONCLUSION: The hepatotoxicity of PDP-R to mice may be reduced by chemical modification with SPDP, but both the affinity of PDP-R to the HCC tissues and ability to kill it may be stronger than that of RT. So this might be a valuable attempt to improve the anticancer activity of RT.

Keywords: ricin/chemistry; ricin/toxicity; liver/ drug effects; liver neoplasms; carcinoma, hepatocellular; glutathione transferase