Efficacy of trimethylselenonium versus selenite in cancer chemoprevention and its modulation by arsenite.

Selenite, which has been demonstrated to be an effective prophylactic agent in experimental carcinogenesis, is metabolized to trimethylselenonium as an excretory product. Previous reports in the literature have shown that arsenite decreases the toxicity of selenite but increases that of trimethylselenonium. The present study was designed to compare the anti-carcinogenic efficacy of selenite and trimethylselenonium and their interactions with arsenite in chemoprevention, using the dimethylbenz[a]anthracene-induced mammary tumor model in rats. The results of this experiment indicated that supplementation of selenite (3 p.p.m. Se) alone produced approximately 50% reduction in tumor yield, and arsenite (5 p.p.m. As) reduced the response to selenite. In contrast, arsenite greatly enhanced the protective effect of trimethylselenonium (40 p.p.m. Se); this combination was nearly as effective as selenite, although either trimethylselenonium or arsenite alone was inactive. Thus, arsenite has the capacity to influence the anti-carcinogenic action of selenium, and can either potentiate or attenuate the protective effect depending on the methylation state of the selenium compound. The metabolism of selenium and its perturbation by arsenite are discussed in relation to the above findings.