Inhibition of DMBA-croton oil two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate through modulation of cutaneous oxidative stress and inhibition of nitric oxide production.

Selenium, an essential micronutrient, plays important roles against different diseases, including several types of cancer. In the present study, antioxidative and chemopreventive properties of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated with a 7,12-dimethylbenz (a) anthracene - croton oil induced two-stage mouse skin carcinogenesis model. The compound was administered orally to carcinogen-treated mice at two different non-toxic doses, 2mg/kg. b.w. and 3mg/kg. b.w. Significant inhibition in the incidence of papilloma formation (53-80%) as well as in the cumulative numbers of papillomas per papilloma bearing mouse were observed in the treated groups as compared to the carcinogen control group. The compound was also found to upregulate significantly different phase II detoxifying enzymes such as glutathione-S-transferase (p<0.01) and superoxide dismutase (p<0.01) in skin cytosol when measured after 15 days and also after 12 weeks of the first 7,12-dimethylbenz (a) anthracene treatment. Lipid peroxidation measured with reference to thiobarbituric acid reactive substances in skin microsomes was significantly inhibited (p<0.05) in a dose dependent manner by diphenylmethyl selenocyanate. Considerable inhibition of the level of nitric oxide production in peritoneal macrophages was observed after 12 weeks (p<0.05). Thus the compound appears to exert chemopreventive activity in terms of papilloma formation, which may be through modulation of cutaneous lipid peroxidation, the phase II detoxifying enzyme system and nitric oxide production.