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-nitrosobis(2-oxopropyl)amine (BOP) is inhibited by orchiectomy and restored by testosterone. These results suggest the involvement of a sex-specific enzyme in BOP bioactivation in rat nasal mucosa. The present study was undertaken to identify this enzyme. Enzyme-linked immunosorbent 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 male rats. Vanillin inhibited the activity of the nasal mucosal enzyme to 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.
Kazakoff
K
K
Eppley Institute for Research in Cancer and Allied Diseases, Omaha, Nebraska.
Iversen
P
P
Lawson
T
T
Baron
J
J
Guengerich
F P
FP
Pour
P M
PM
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002369:Castration; D002471:Cell Transformation, Neoplastic; D019392:Cytochrome P-450 CYP2E1; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D016296:Mutagenesis / Q000187:drug effects; D009297:Nasal Mucosa / Q000201:enzymology*; D009602:Nitrosamines / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood
D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D009602:Nitrosamines; D013739:Testosterone; C013622:nitrosobis(2-oxopropyl)amine; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating