Determination of DNA single strand breaks and selective DNA amplification by N-nitrodimethylamine and analogs, and estimation of the indicator cells' metabolic capacities.
N-nitrodimethylamine is metabolized oxidatively to N-nitrohydroxymethylmethylamine, which decomposes to yield formaldehyde and N-nitromethylamine. All four compounds and N-nitromethylamine were tested for their ability to induce DNA single strand breaks in hepatocytes and in SV 40-transformed Chinese hamster embryo cell lines. Only the two monoalkylnitramines were positive. They induced single strand breaks in hepatocytes, but were not effective in the other cells. Formaldehyde and N-nitrohydroxymethylmethylamine were toxic to the cells. None of the compounds tested was able to induce selective DNA amplification in the two transformed cell lines. Enzymes involved in drug metabolism were assayed in the hamster cell lines. The activity of UDP-glucuronosyltransferase and cytosolic epoxide hydrolase were not detectable. N-nitrodimethylamine demethylation was low. The content of reduced glutathione and the activities of glutathione transferase and membrane bound epoxide hydrolase were comparable to values obtained in the rat liver.
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004123:Dimethylamines / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects / Q000201:enzymology; D005557:Formaldehyde / Q000378:metabolism / Q000633:toxicity; D005784:Gene Amplification / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D013539:Simian virus 40
D004277:DNA, Single-Stranded; D004123:Dimethylamines; D005557:Formaldehyde; C013962:dimethylnitramine