Cytochrome P450-dependent metabolism of trichloroethylene: interindividual differences in humans.
Lipscomb-JC; Garrett-CM; Snawder-JE
Toxicol Appl Pharmacol 1997 Feb; 142(2):311-318
Interindividual differences in cytochrome-P450 dependent metabolism of trichloroethylene (79016) (TRI), an industrial solvent and common groundwater contaminant, were assessed in humans. The degree to which the step whereby TRI is metabolized through chloral-hydrate (302170) to compounds such as trichloroacetic-acid (76039) and dichloroacetic-acid (79436) varies between individuals was evaluated in a sample set of 23 human hepatic microsomal fractions. Significant variability in TRI metabolism between samples was observed. TRI metabolism was dependent on cytochrome-P450 2E1 (CYP2E1). Microsomal chloral-hydrate formation was correlated with the activity toward routine CYP2E1 substrates and with immunologically detectable CYP2E1 protein. CYP2E1 appeared to be the predominant form of cytochrome-P450 responsible for TRI metabolism in humans; it catalyzed more than 60% of total microsomal TRI metabolism. The involvement of other CYP forms was also assessed; CYP1A and CYP3A formed chloral-hydrate at much lower rates than CYP2E1. The authors conclude that humans are not uniform in their capacity for cytochrome-P450 dependent metabolism of TRI; increased CYP2E1 activity may increase susceptibility to TRI induced toxicity.
Solvents; Liver-microsomal-metabolism; Industrial-hazards; Risk-analysis; Hepatotoxicity; Enzyme-activity; Oxidative-metabolism; Toxicology; Chlorinated-ethylenes
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Toxicology and Applied Pharmacology