Activity of methylated forms of selenium in cancer prevention.
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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Department of Breast Surgery, Roswell Park Memorial Institute, Buffalo, New York 14263.
Ganther
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D001622:Betaine / Q000031:analogs & derivatives* / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D054833:Isoindoles; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000517:prevention & control; D016566:Organoselenium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D020887:Selenious Acid; D012643:Selenium / Q000378:metabolism* / Q000494:pharmacology
D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D001622:Betaine; C042986:ebselen; D015127:9,10-Dimethyl-1,2-benzanthracene; C048731:selenobetaine; D020887:Selenious Acid; D012643:Selenium; D001151:Arsenic