Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1772, Issue 1, Pages 48-59Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2006.10.019
Keywords
vanadium; hepatocarcinogenesis; DNA adduct; ethylguanines; 8-OHdGs; DNA strand-break
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Carcinogen-induced formation of DNA adducts and other types of DNA lesions are the critical molecular events in the initiation of chemical carcinogenesis and modulation of such events by chemopreventive agents could be an important step in limiting neoplastic transformation in vivo. Vanadium, a dietary micronutrient has been found to be effective in several types of cancers both in vivo and in vitro and also possesses profound anticarcinogenicity against rat models of mammary, colon and hepatocarcinogenesis. Presently, we report the chemopreventive potential of vanadium on diethylnitrosaminc (DEN)-induced early DNA damages in rat liver. Hepatocarcinogenesis was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal (i.p.) injection of DEN (200 mg/kg body weight) at week 4. There was a significant induction of tissue-specific ethylguanines, steady elevation of modified DNA bases 8-hydroxy-2'-deoxyguanosines (8-OHdGs) (P < 0.0001; 89.93%) along with substantial increment of the extent of single-strand breaks (SSBs) (P < 0.0001) following DEN exposure. Supplementation of 0.5 ppm of vanadium throughout the experiment abated the formations of O-6-ethylguanines and 7-ethylguanines (P < 0.0001; 48.71% and 67.54% respectively) 8-0HdGs(P < 0.0001;81.37%), length:width (L:W) of DNA mass (P < 0.011- 62.12%) and the mean frequency of tailed DNA (P < 0.001; 53.58%), and hepatic nodulogenesis in preneoplastic rat liver. The study indicates that 0.5 ppm vanadium is potentially and optimally effective, as derived from dose-response studies, in limiting early molecular events and preneoplastic lesions, thereby modulating the initiation stage of hepatocarcinogenesis. Vanadium is chemopreventive against DEN-induced genotoxicity and resulting hepatocellular transformation in rats. (c) 2006 Published by Elsevier B.V.
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