Expression of cytochrome CYP2B1/2 in nonpregnant, pregnant and fetal rats exposed to tobacco smoke

Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke obtained from non-filter cigarettes. During the exposure, concentration of tobacco smoke was monitored indirectly by measuring the CO level (1500 mg/ m(3) air). The efficacy of exposure was assessed by measuring urine nicotin e and cotinine levels. Cigarette smoke did not change total cytochrome P450 and b(5) protein levels in any of the organs studied, and most of these or gans did not show any changes in the activity of reductases associated with these cytochromes. Following exposure to tobacco smoke, fetal rat liver ex pressed CYP2B1/2 protein; in newborns (day 1) both liver and lung showed CY P2B1/2 protein expression and very low pentoxyresorufin O-dealkylase activi ty. Western blot analysis of adult liver, lung, heart, but not of brain mic rosomes, showed that tobacco smoke induced CYP2B1/2 in both nonpregnant and pregnant rats, though its expression was lower in the livers and hearts of pregnant females. In the rat and human placenta, neither rat CYP2B1/2 nor human CYP2B6 showed basal or tobacco smoke-induced expression at the protei n level. This study shows clearly that the expression of CYP2B1/2, which me tabolizes nicotine and some drugs and activates carcinogens, is controlled in rats by age-, pregnancy-, and tissue-specific regulatory mechanisms.