Covalent binding of trichloroethylene to proteins in human and rat hepatocytes.
The environmental contaminant and occupational solvent trichloroethylene is metabolized to a reactive intermediate that covalently binds to specific hepatic proteins in exposed mice and rats. In order to compare covalent binding between humans and rodents, primary hepatocyte cultures 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, distinctively different 47 kDa adduct was detected in human hepatocytes. The 50 kDa adduct in rat hepatocytes was found to comigrate on SDS-PAGE with cytochrome P450 2E1 (CYP2E1), while the adduct found in humans did not 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, but not humans, that one of the targets is CYP2E1.
University of Arkansas for Medical Science, Department of Pharmacology and Toxicology, Little Rock, USA.
J M
JM
Griffin
J C
JC
Lipscomb
N R
NR
Pumford
D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D006801:Humans; D007120:Immunochemistry; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000378:metabolism*; D014241:Trichloroethylene / Q000097:blood / Q000378:metabolism*
D012997:Solvents; D014241:Trichloroethylene; D019392:Cytochrome P-450 CYP2E1