DIFFERENTIAL XENOBIOTIC INDUCTION OF CYP2A5 IN MOUSE-LIVER, KIDNEY, LUNG, AND OLFACTORY MUCOSA

The effects of pyrazole, which is known to induce hepatic cytochrome P 4502A5 (CYP2A5) through posttranscriptional mechanisms, on the level o f CYP2A5 in liver and extrahepatic tissues were examined in this study . Intraperitoneal administration of pyrazole at 200 mg/kg for 3 days i nduced CYP2A4/5 mRNAs and proteins and microsomal coumarin 7-hydroxyla tion activity in liver and kidney of C57BL/6 mice. A marginal increase (30%) in CYP2A4/5 mRNAs was also observed in the olfactory mucosa but not in the lung, and no increase in CYP2A4/5 proteins or microsomal c oumarin 7-hydroxylation activity was observed in either the olfactory mucosa or lung. CYP2A4/5 proteins were not detected on immunoblots in other tissues examined, including breast, bone marrow, testis, prostat e, ovary, and uterus from control or pyrazole-treated mice. On the oth er hand, pyrazole treatment induced CYP2E1 in the olfactory mucosa as well as in liver and kidney, indicating that the olfactory mucosa was exposed to pyrazole. The lack of CYP2A inducibility in the olfactory m ucosa was also observed for several other known inducers of hepatic CY P2A5, including cobaltous chloride, stannous chloride, griseofulvin, t hioacetamide, and aminotriazole. These results suggest that the mechan isms involved in the induction of hepatic and renal CYP2A5 by pyrazole and other xenobiotic compounds may be tissue-specific.