Vanadium chemoprevention of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis: probable involvement of representative hepatic phase Iand II xenobiotic metabolizing enzymes

Vanadium, a non-platinum group metal and dietary micronutrient, is now prov ing to act as a promising antitumor agent. The present study was conducted to ascertain its antineoplastic potential against an experimental mammary c arcinogenesis. Female Sprague-Dawley rats, at 50 days of age, were treated with 7,12-dimethylbenz(a)anthracene (DMBA) (0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion. Vanadium (ammonium monovanad ate) at the concentration of 0.5 ppm was supplemented in drinking water and given ad libitum to the experimental group immediately after the carcinoge n treatment and it continued until the termination of the study (24 weeks f or histological and biochemical observations and 35 weeks for morphological findings). It was found that vanadium treatment brought about a substantia l protection against DMBA-induced mammary carcinogenesis. This was evident from histological findings that showed no sign of hyperplasia or abnormalit y after vanadium treatment. There was a significant reduction in incidence (P < 0.05), total number, multiplicity (P < 0.01) and size of palpable mamm ary tumors and delay in mean latency period of tumor appearance (P < 0.001) following vanadium supplementation compared to DMBA control. From the cumu lative results of various hepatic biochemical indices namely, lipid peroxid ation, reduced glutathione level, superoxide dismutase activity, cytochrome P450 content and glutathione S-transferase activity, the anticarcinogenic potential of vanadium was well reflected through stabilization of these par ameters. Results of the study indicate that the anticarcinogenic activity o f vanadium during DMBA-initiated mammary carcinogenesis is mediated through alteration of hepatic antioxidant status as well as modulation of phase I and II drug metabolizing enzymes. On the basis of the observed results, van adium can be considered as a readily available, promising and novel cancer chemopreventive agent.