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

Abstract

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.