Ring oxidation of 6-nitrobenzo (a) pyrene by female mouse liver.

C Raha, D Williamson, M Hart-Anstey, T Maiefski, S J Stohs, E Bresnick

Index: Res. Commun. Chem. Pathol. Pharmacol. 58(1) , 63-74, (1987)

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Abstract

6-Nitrobenzo (a) pyrene (6-NBaP) is an environmental contaminant. In bacterial mutagenesis assays, 6-NBaP requires rat liver S9 enzymes for its activity. Chemical characterization of metabolites of 6-NBaP produced by male rat liver microsomes showed them to be ring-hydroxylated (both mono- and dihydroxy) derivatives. Thus, metabolic activation of 6-NBaP may occur via ring oxidation. It has been shown by others that when injected intraperitoneally into newborn mice, 6-NBaP was carcinogenic to male, but not to female, mouse liver. The nitro-hydrocarbon was not carcinogenic to the lungs of either sex. We have examined the metabolism of 6-NBaP by the liver of a non-susceptible female mouse and observed the formation of ring-hydroxylated metabolites of 6-NBaP. In view of this observation, we suggest that ring hydroxylation alone may not be sufficient in explaining the carcinogenicity of 6-NBaP in male and not in female mice.