Vanadium chemoprevention of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis: probable involvement of representative hepatic phase I and II xenobiotic metabolizing enzymes.
Vanadium, a non-platinum group metal and dietary micronutrient, is now proving to act as a promising antitumor agent. The present study was conducted to ascertain its antineoplastic potential against an experimental mammary carcinogenesis. 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 monovanadate) at the concentration of 0.5 ppm was supplemented in drinking water and given ad libitum to the experimental group immediately after the carcinogen treatment and it continued until the termination of the study (24 weeks for histological and biochemical observations and 35 weeks for morphological findings). It was found that vanadium treatment brought about a substantial protection against DMBA-induced mammary carcinogenesis. This was evident from histological findings that showed no sign of hyperplasia or abnormality after vanadium treatment. There was a significant reduction in incidence (P < 0.05), total number, multiplicity (P < 0.01) and size of palpable mammary tumors and delay in mean latency period of tumor appearance (P < 0.001) following vanadium supplementation compared to DMBA control. From the cumulative results of various hepatic biochemical indices namely, lipid peroxidation, 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 parameters. Results of the study indicate that the anticarcinogenic activity of 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, vanadium can be considered as a readily available, promising and novel cancer chemopreventive agent.
Bishayee
A
A
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India. bishayan@umdnj.edu
Oinam
S
S
Basu
M
M
Chatterjee
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005260:Female; D005978:Glutathione / Q000032:analysis; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014639:Vanadium / Q000494:pharmacology* / Q000627:therapeutic use; D015262:Xenobiotics / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D015262:Xenobiotics; D014639:Vanadium; D015127:9,10-Dimethyl-1,2-benzanthracene; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione