Biological activities of trimethylselenonium as influenced by arsenite.
The present study was designed to evaluate three biological activities of trimethylselenonium (TMSe+): anticarcinogenicity, toxicity, and nutritional availability. These experiments were carried out in female rats both in the presence and absence of arsenite because arsenite is known to affect selenium metabolism. Supplementation with TMSe+ by itself in the diet, at levels of 20, 40, or 80 ppm Se, did not offer any protection against mammary carcinogenesis induced by dimethylbenz(a)anthracene. On the other hand, the coadministration of arsenite (5 ppm As) with the two higher levels of TMSe+ resulted in significant tumor suppression. In the acute toxicity experiment, rats were injected subcutaneously with 0.5 or 1 mg Se/kg, preceded 15 minutes earlier by arsenite at doses of 0.5, 1, or 2 mg As/kg. Although treatment with TMSe+ or arsenite alone did not produce any sign of toxicity, a synergistic toxic effect was evident with the combination. Regarding the ability of TMSe+ to restore hepatic glutathione peroxidase following selenium depletion, it was found that a dietary level of 40 ppm Se was necessary for complete recovery. The nutritional biopotency of TMSe+ was not sensitive to either up- or down-regulation by arsenite under conditions where arsenite also enhanced the anticarcinogenic activity of TMSe+. The contrasting effects of arsenite on these two end points suggest that different forms of selenium are involved. It is hypothesized that arsenite might increase the production of a critical metabolite from methylated selenides. However, there is no clear evidence at the present time to suggest whether the same intermediate(s) is responsible for both anticarcinogenicity and toxicity.
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Department of Breast Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263.
Ganther
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D001151:Arsenic / Q000494:pharmacology*; D018053:Arsenites; D004032:Diet; D004357:Drug Synergism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D018036:Selenium Compounds
D016588:Anticarcinogenic Agents; D018053:Arsenites; D018036:Selenium Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene; D005979:Glutathione Peroxidase; D012643:Selenium; C015001:arsenite; D001151:Arsenic; C003717:trimethylselenonium