| 3619641 |
Appel KE, Gorsdorf S, Scheper T, Bauszus M, Hildebrandt AG: Enzymatic denitrosation of diphenylnitrosamine: activation or inactivation?. Arch Toxicol. 1987;60(1-3):204-8.
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. |
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