ISSN:
1432-1335
Schlagwort(e):
N-Nitrosamines
;
Metabolism
;
Denitrosation
;
Activation
;
Inactivation
;
Single strand breaks
;
Hepatocytes
;
Chinese hamster V 79 cells
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary 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 was 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 and some of the metabolites were also tested. One metabolite was identified as diphenylamine whereas the others were identified as a ring-hydroxylated derivative of diphenylamine and its corresponding quinoneimine. Diphenylhydroxylamine which was not detected in the microsomes as a metabolite produced a significant amount of DNA single strand breaks in V 79 cells. When diphenylhydroxylamine was incubated with microsomes electron spin resonance spectrum was observed which indicated the formation of the diphenylnitroxide radical. This radical seems to be mediated by auto-oxidation rather than by enzymatic catalysis. Whether diphenylhydroxylamine might be responsible for the observed genetoxic effects of nitrosodiphenylamine assumed to be produced via active oxygen species is discussed.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00391434
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