COVALENT BINDING OF TRICHLOROETHYLENE TO PROTEINS IN HUMAN AND RAT HEPATOCYTES

The environmental contaminant and occupational solvent trichloroethyle ne is metabolized to a reactive intermediate that covalently binds to specific hepatic proteins in exposed mice and rats. In order to compar e covalent binding between humans and rodents, primary hepatocyte cult ures were exposed to vaporized trichloroethylene at 0-10 000 parts per million for up to 2 h. Immunochemical detection of three major dose- and time-dependent trichloroethylene protein adducts at 50, 52 and 100 kDa was demonstrated in the rat hepatocytes, while a single, distinct ively different 47 kDa adduct was detected in human hepatocytes. The 5 0 kDa adduct in rat hepatocytes was found to comigrate on SDS-PAGE wit h cytochrome P450 2E1 (CYP2E1), while the adduct found in humans did n ot comigrate with CYP2E1. These data show that reactive metabolites of trichloroethylene can be formed in human and rat hepatocytes and bind covalently to discrete hepatic proteins, and suggests that in rats, b ut not humans, that one of the targets is CYP2E1. (C) 1998 Elsevier Sc ience Ireland Ltd. All rights reserved.