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.