EFFECT OF CIGARETTE-SMOKE ON HEPATIC AND PULMONARY CYTOCHROMES P450 IN MOUSE - EVIDENCE FOR CYP2E1 INDUCTION IN LUNG

Pulmonary and liver microsomes of male NMRI mice were used to study th e inductive effect of cigarette smoke on various cytochrome P450 isofo rms implicated in precarcinogen and premutagen bioactivation. The enzy matic activities catalyzed by CYP1A1, CYP2B, CYP2C, CYP2D, CYP2E1 and CYP3A were induced in liver microsomes. Immunoquantification of lung a nd liver CYP1A1, 2E1 and 3A demonstrated that 1) CYP1A1 was induced in lung and liver, 2) CYP3A subfamily was induced in liver and not detec ted in lung, 3) CYP2E1 was slightly induced in liver whereas its pulmo nary expression was more largely increased (6.8 fold) than CYP1A1 (2.0 fold). This latter data suggests that CYP2El, which is known to be ex pressed in human lung, could actively participate in pulmonary carcino genesis induced by cigarette smoke. (C) 1994 Academic Press, Inc.