EFFECT OF ETHANOL ON CHCL3 METABOLISM IN HEPATIC MICROSOMES FROM OSBORNE-MENDEL RATS

The treatment of Osborne-Mendel rats with ethanol in drinking water fo r 2 weeks resulted in a 3-fold increase of hepatic microsomal hydroxyl ation of both p-nitrophenol and aniline, two substrates considered hig hly selective for P4502E1. No other forms of P450 seemed to be affecte d. These results, confirmed by the immunoblot analysis of microsomal p rotein, showed an induction of P4502E1 The levels of total covalent bi nding to microsomal phospholipid due to (CHCl3)-C-14 reactive intermed iates in ethanol-pretreated microsomes were identical to those measure d in microsomes from untreated rats at any pO(2). The distribution of radioactivity obtained after transmethylation of the adducts of (CHCl3 )-C-14 intermediates with microsomal phospholipids (PL) indicated that binding to fatty acyl chains (due to .CHCl2 radicals.) increased with decreasing pO(2). On the contrary. the binding to polar heads due to phosgene decreased. The ethanol treatment did not affect binding to ei ther PL moieties. These results indicated that, in our experimental co nditions, the in vitro production of both oxidative and reductive inte rmediates of CHCl3 in the liver of Osborne-Mendel rats were not influe nced by ethanol consumption.