Enzymatic denitrosation of diphenylnitrosamine: activation or inactivation?
Nitrosodiphenylamine was tested for induction of DNA single strand breaks in rat hepatocytes and Chinese hamster V 79 cells with the alkaline filter elution assay. While in rat hepatocytes DNA damage could be observed, negative results were obtained in V 79 cells. In view of the metabolic capacity of hepatocytes and the chemical structure of nitrosodiphenylamine, it seems likely that cytochrome P-450-dependent, reductive denitrosation might be necessary for exerting this effect. Therefore the metabolism of nitrosodiphenylamine was investigated in phenobarbital-induced mouse liver microsomes. Various metabolites were determined by HPLC. One metabolite was identified as diphenylamine, whereas the others were characterized as p-hydroxydiphenylamine and its corresponding quinoneimine. It is postulated that diphenylhydroxylamine, which is not found as a metabolite, might be involved in exerting the observed genetoxic effects.
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D008862:Microsomes, Liver / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D009602:Nitrosamines; D009603:Nitroso Compounds; D004247:DNA; C023649:N-nitrosodiphenylamine