Carcinogen-induced early molecular events and its implication in the initiation of chemical hepatocarcinogenesis in rats: chemopreventive role of vanadium on this process.

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 diethylnitrosamine (DEN)-induced early DNA damages in rat liver.

Vanadium limits the expression of proliferating cell nuclear antigen and inhibits early DNA damage during diethylnitrosamine-induced hepatocellular preneoplasia in rats.

Previous studies from our laboratory have shown that vanadium stabilizes xenobiotic metabolizing enzymes and antioxidant status and suppresses DNA-protein crosslinks during chemically-induced hepatocarcinogenesis in rats. In the present study, we have further investigated the in vivo antitumor potential of this micronutrient by determining the effect of 0.5 ppm vanadium in drinking water on biomarkers for the early stages of hepatocarcinogenesis; the biomarkers included gamma-glutamyl transpeptidase (GGT)-positive foci and glycogen-storage foci, in situ expression of proliferating cell nuclear antigen (PCNA), and genotoxic DNA damage assessed by the alkaline Comet assay.