title: Short-term effects of chlorophenols on the function and viability of primary cultured rat hepatocytes.
abstract: Primary cultured rat hepatocytes were used as an experimental model to detect adverse effects of five chlorophenols (CP) in vitro (penta-CP, 2,3,4,5-tetra-CP, 2,4,5,-tri-CP, 2,4-di-CP, and 4-mono-CP). Monolayer cultures were exposed to the test compounds for 1 h, and concentration-response curves were established with respect to the effects on phase I and phase II metabolism of 7-ethoxycoumarin (7-EC) and on cellular ATP content. All CP tested inhibited the O-dealkylation of 7-EC, with half-maximum effective concentrations (EC50) ranging from about 36 microM for the three highest chlorinated phenols to 215 microM for 4-mono-CP, which proved to be least effective. The subsequent conjugation of the primary metabolite 7-hydroxycoumarin was even more sensitive towards CP exposure than the O-deethylation process. The concentrations which reduced the percentage of conjugated metabolite to 50% of the respective control cultures ranged from 7 microM for penta-CP to 48 microM for 4-mono-CP. Treatment of cultured hepatocytes with CP additionally resulted in a depletion of cellular ATP at EC50 concentrations ranging from 6 microM for penta-CP to 1330 microM for 4-mono-CP. Cellular viability, as measured by the leakage of lactate dehydrogenase from the cells, was not affected by any of the CP within the 1-h exposure period.
authors: Christian-Albrechts-Universität, Kiel, Federal Republic of Germany.
authors: C
authors: C
authors: Aschmann
authors: T
authors: T
authors: Stork
authors: O
authors: O
authors: Wassermann
mesh_terms: D015660:7-Alkoxycoumarin O-Dealkylase; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002733:Chlorophenols / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010105:Oxygenases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002733:Chlorophenols; D011506:Proteins; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase