| Abstrakt: |
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 (EC) ranging from about 36 μM for the three highest chlorinated phenols to 215 μM 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 μM for penta-CP to 48 μM for 4-mono-CP. Treatment of cultured hepatocytes with CP additionally resulted in a depletion of cellular ATP at EC concentrations ranging from 6 μM for penta-CP to 1330 μM 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. [ABSTRACT FROM AUTHOR] |
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