title: Characterization of the metabolic interaction between trihalomethanes and chloroacetic acids using rat liver microsomes.
abstract: The aim of this study was to investigate the in vitro metabolism of trihalomethanes (THMs) in the presence of trichloroacetic acid (TCA), dichloracetic acid (DCA), monochloroacetic acid (MCA), and 4-methylpyrazole (4-MP) using liver microsomes from male Sprague-Dawley rats. Using the vial equilibration technique, initial experiments were carried out with starting concentrations of approximately 40 ppm THMs and 12-22 mM chloroacetic acids. The results indicated a mutual metabolic inhibition between THMs present as binary or quaternary mixtures. Although DCA and MCA had no influence on THMs, TCA produced a marked inhibition of the metabolism of all THMs: chloroform (CHCl3) (55%), bromodichloromethane (BDCM) (34%), dibromochloromethane (DBCM) (30%), and bromoform (TBM) (23%). The presence of 4-MP also reduced THM metabolism, the importance of which decreased in the following order: CHCl3 > BDCM > DBCM = TBM. In further vial equilibration experiments, using 9-140 ppm as starting concentrations of THMs, enzyme kinetic parameters (i.e., Michaelis constant, K(m), and maximum velocity, V(max)) were determined both in the absence and in the presence of TCA (12.2 mM). Results are consistent with a competitive inhibition between TCA and CHCl3, whereas the metabolic inhibition of BDCM and TMB by TCA was non-competitive. As for DBCM, results suggest a more complex pattern of inhibition. These results suggest that CYP2E1 is involved in the metabolism of THMs as well as in the metabolic interaction between THMs and TCA.
authors.affiliation: TOXHUM (Groupe de recherche en toxicologie humaine), Département de Santé Environnementale et Santé au Travail, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: St-Pierre
authors.forename: Kannan
authors.initials: K
authors.lastname: Krishnan
authors.forename: Robert
authors.initials: R
authors.lastname: Tardif
mesh_terms: D000085:Acetates / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000494:pharmacology*; D004203:Disinfection; D004347:Drug Interactions; D005260:Female; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D022882:Trihalomethanes / Q000378:metabolism* / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity
chemical_list: D000085:Acetates; D022882:Trihalomethanes; D014874:Water Pollutants, Chemical; C006972:chloroacetic acid; D019392:Cytochrome P-450 CYP2E1