Inhibitory effects of selenium on 1,2-dimethylhydrazine and methylazoxymethanol colon carcinogenesis: correlative studies on selenium effects on the mutagenicity and sister chromatid exchange rates of selected carcinogens.
Selenium (Se) inhibition of either the activation of test compounds and/or mutagenic events elicited by activated compounds is suggested by experimental rat assays, mutagenesis assays, and assays with human lymphocytes in culture. The colon tumor incidence in 1,2-dimethylhydrazine (DMH)-treated rats was reduced from 87% to 40% by 4 ppm Se supplements in the drinking water. Supplemental Se decreased the total number of colon tumors induced by DMH more than three-fold and by methylazoxymethanol (MAM) almost two-fold. Coexposure of Salmonella typhimurium TA 1538 to an effective molar ratio of Se/2-acetylaminofluorene=10, Se/N-OH-acetylaminofluorene=10 and SE/N-OH-aminofluorene=300 reduced the mutagenicity to 65, 68, and 61% of their respective controls with mutagen alone. With a molar ratio of Se/N-OH-AAF=100, Se reduced the activity to 28% of the mutagenicity of N-OH-AAF alone. Preliminary data indicating MAM is mutagenic in S. typhimurium TA 1535 and His G 46(6837) are presented. In toxicity studies exposure of human lymphocyte cultures to 1.3 X 10(-9) to 1.6 X 10(-5) M Se yielded sister chromatid exchange (SCE) rates equivalent to background levels of 6--7 SCE per cell. The SCE frequencies of lymphocytes cultured with Se and selected carcinogens are discussed.
D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D002877:Chromosomes, Human; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004127:Dimethylhydrazines / Q000037:antagonists & inhibitors; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000037:antagonists & inhibitors; D009153:Mutagens / Q000037:antagonists & inhibitors*; D051381:Rats; D011995:Recombination, Genetic / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000235:genetics; D012643:Selenium / Q000494:pharmacology*
D002273:Carcinogens; D004127:Dimethylhydrazines; D009153:Mutagens; D008746:Methylazoxymethanol Acetate; D012643:Selenium