Rk. Sindhu et al., DEPRESSION OF HEPATIC CYTOCHROME-P450 MONOOXYGENASES AFTER CHRONIC ENVIRONMENTAL TOBACCO-SMOKE EXPOSURE OF YOUNG FERRETS, Toxicology letters, 76(3), 1995, pp. 227-238
Six-week-old ferrets were exposed head-only to clean air or environmen
tal tobacco smoke (ETS) for 2 h/day, 5 days a week for a total of 8 we
eks, Exposure to ETS caused a significant reduction in the levels of h
epatic microsomal cytochrome P450 and P450 reductase activity in both
the male and female ferrets. The content of cytochrome b(5) and the ac
tivity of its reductase were significantly reduced in the hepatic micr
osomes of female ferrets. 7-Ethoxycoumarin O-deethylase activity and c
ytochrome P450 (CYP) 1A protein were markedly decreased in the hepatic
microsomes of both the male and female ferrets after ETS exposure. In
accord with the downregulation of P450, total metabolites formed from
benzo[a]pyrene were significantly reduced in the liver homogenates of
ETS-exposed animals. Similarly, sum total of free +)-anti-benzo[a]pyr
ene-7,8-dihydrodiol-10-epoxide, glutathione conjugates and DNA-bound m
etabolites formed from precursor (-)-7R-trans-benzo[a]pyrene-7,8-dihyd
rodiol showed marked reduction in both the male and female ferrets aft
er ETS exposure in a dose-response manner. This is the first report sh
owing downregulation of hepatic P450 and accompanying benzo[a]pyrene m
etabolism after tobacco smoke exposure which apparently occurred after
an initial upregulation of these parameters