ACETONE-DEPENDENT REGULATION OF CYTOCHROMES P4502E1 AND P4502B1 IN RAT NASAL-MUCOSA

The inducibility and molecular regulation of cytochrome P4502E1 (CYP2E 1) has been examined in nasal mucosa of rats after acetone treatment a nd compared to that of cytochrome P4502B1 (CYP2B1). Twenty-four hours following treatment with acetone (5 mL/kg) for 2 days, the amount of C YP2E1 as well as the rate of microsomal I-nitrophenol hydroxylase acti vity had increased by a factor of 2-3, in microsomes isolated from nas al mucosa. The increase in CYP2E1 was accompanied by a corresponding i ncrease of CYP2E1 mRNA, as determined by northern and slot blot analys es. In contrast, hepatic and renal CYP2E1 mRNA, studied in the same ra ts, did not increase, despite the fact that the amount of CYP2E1 was i ncreased 3- and 5-fold, respectively. The amount of CYP2B1, an isozyme known as acetone-inducible in other tissues, decreased significantly by acetone, as detected by immunoblot analysis. After 48 hr, the amoun t of CYP2E1 enzyme, the level of CYP2E1 mRNA and the rate of 4-nitroph enol hydroxylase activity had returned to normal levels, whereas in li ver and kidneys the immunoreactive protein remained 3-4-fold higher th an control. The results indicate that acetone does not regulate CYP2E1 in nasal mucosa by post-translational mechanisms, in contrast to the situation observed in liver and kidneys. This indicates a tissue-speci fic expression of post-translational regulatory systems responsible fo r P450 stabilization. Furthermore, nasal CYP2B1 also seems to be regul ated in a tissue-specific manner by acetone.