EFFECT OF CIGARETTE-SMOKE ON UDP-GLUCURONOSYLTRANSFERASE ACTIVITY ANDCYTOCHROME-P450 CONTENT IN LIVER, LUNG AND KIDNEY MICROSOMES IN MICE

The effect of cigarette smoke on the expression of several cytochromes P450 (CYP) and UDP-glucuronosyl-transferases (UGT) was studied in mic e. The animals were exposed to cigarette smoke for 4 to 30 days. Enzym atic activities supported by CYP1A1, 1A2, 2B, 2E1 and the glucuronidat ion activity toward phenols were measured in lung, liver and kidney mi crosomes. Cigarette smoke induced several CYPs, especially in lung. CY P2E1 was more induced than CYP1A1 in this organ. The expression of CYP 2E1 was also increased in kidney (5.6 times after 30 days). The glucur onidation in kidney was non-sensitive to the treatment whatever substr ate used. In contrast, this activity was enhanced in liver and particu larly in lung, in which the glucuronidation of 1-naphthol and 2-hydrox ybiphenyl was increased by 122 and 180%, respectively. Interestingly, the limes of induction differed according to the substrate used, thus suggesting the presence of different UGTs active toward phenols that w ere differentially affected by cigarette smoke. The UGT activities tow ard phenols were low in lung, when compared with those measured in liv er or kidney. In conclusion, cigarette smoke greatly; affected both gl ucuronidation activity and the hydroxylation reactions supported by CY Ps in mouse liver and lung.