Selenium and the acute effects of the carcinogens, 2-acetylaminofluorene and methylazoxymethanol acetate.
Selenium inhibits the development of 2-acetylaminofluorene-induced hepatic tumors and methylazoxymethanol-induced colon tumors. It has been suggested that selenium exerts these protective effects by inhibiting metabolic activation of the carcinogen. We have studied the effects of selenium upon the acute inhibition of RNA and DNA synthesis induced by 2-acetylaminofluorene or methylazoxymethanol in intact liver, regenerating liver, and colon of weanling male Sprague-Dawley rats. Some animals received selenium in the drinking water (4 ppm) for 1 week, while others received a single injection of selenium (1 mg/kg i.p.) prior to being treated with the carcinogens. No protection against the effects of the carcinogens on RNA or DNA synthesis was noted with either treatment of selenium. Disulfiram did protect against the 2-acetylaminofluorene-induced inhibition of hepatic RNA synthesis, and pyrazole prevented the inhibition of RNA synthesis induced by methylazoxymethanol in both liver and colon. Serum selenium levels are reported. The data indicate that selenium does not influence the acute alterations induced by the carcinogens 2-acetylaminofluorene or methylazoxymethanol and suggest that the tumor-preventive effects of selenium are probably due to a mechanism other than interference with carcinogen activation and interaction with cellular macromolecules.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D003106:Colon / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004347:Drug Interactions; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014158:Transcription, Genetic / Q000187:drug effects
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate; D012313:RNA; D004247:DNA; D015073:2-Acetylaminofluorene; D012643:Selenium