The anticarcinogenic activity of selenium in animal models is well established. The active forms of selenium involved have not been identified to date, but conversion of selenium via hydrogen selenide (H2Se) to methylated forms such as dimethylselenide and trimethylselenonium ion is an important metabolic fate. By controlling the entry of selenium into various points within this pathway through selection of appropriate starting compounds, it is possible to pinpoint more closely the form(s) of selenium responsible for its anticarcinogenic activity. Selenobetaine in the chloride form [(CH3)2Se+CH2COOH] and its methyl ester are extensively metabolized in the rat to mono-, di-, and trimethylated selenides, largely bypassing the inorganic H2Se intermediary pool. The chemopreventive efficacy of these selenobetaines was determined at 1 and 2 ppm selenium supplemented in the diet throughout the duration of the experiment using the dimethylbenz(a)anthracene induced mammary tumor model in rats. There was a dose-dependent inhibitory response to both compounds, and they appeared to be slightly more active than selenite. These doses were without any adverse effects on the animals. Coadministration of selenobetaine with arsenite (5 ppm arsenic) enhanced the tumor-suppressive effect of selenobetaine, although arsenic by itself was totally inactive. Arsenite is known to inhibit certain steps in selenium methylation. The substantial prophylactic efficacy of methylated selenides and the enhancement by arsenite suggest that partially methylated forms of selenium may be directly involved in the anticarcinogenic action of selenium.

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This project was supported by Grant CA45164 from the National Cancer Institute, NIH, and by the College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI. Preliminary reports were presented at the 80th annual meeting of the American Association for Cancer Research, San Francisco, May 1989, and at the Joint AACR/Japanese Cancer Association Meeting in Honolulu, May 1989.

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