INVOLVEMENT OF CYTOCHROME-P450 2E1-LIKE ISOFORM IN THE ACTIVATION OF N-NITROSOBIS(2-OXOPROPYL)AMINE IN THE RAT NASAL-MUCOSA

Induction of tumours in the nasal olfactory region of MRC rats by N-ni trosobis(2-oxopropyl)amine (BOP) is inhibited by orchiectomy and resto red by testosterone. These results suggest the involvement of a sex-sp ecific enzyme in BOP bioactivation in rat nasal mucosa. The present st udy was undertaken to identify this enzyme. Enzyme-linked immunosorben t assay (ELISA) and the metabolism of known substrates (p-nitrophenol) pointed to a microsomal cytochrome P450 (P450) 2E1-like isoform as a candidate enzyme. A correlation was found between the enzyme activity in nasal mucosal microsomes and serum testosterone levels. Four times more activity was detected in the nasal mucosa than in the liver of ma le rats. Vanillin inhibited the activity of the nasal mucosal enzyme t o a greater extent than that of the liver enzyme. The overall results suggest that a nasal mucosal P450 2E1-like isoform is involved in BOP metabolism.