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KMID : 0382420030290030009
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Korean Journal of Environmental Health Society
2003 Volume.29 No. 3 p.9 ~ p.15
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Differential Role of Solvents on Human Cytochrome P450 2E1 Activity in Intact HepG2 Cells
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Choi Dal-Woong
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Abstract
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The modification of CYP2E1 activity is a matter of considerable interest because of its role in the metabolic activation of a variety of environmental toxicants. In the present study, the time-course of changes in human CYP2E1 activities was determined following treatment with solvents (acetone, dimethylsulphoxide or pyridine) using intact HepG2 cells transfected by human CYP2E1. Hydroxylation of chlorzoxazone was used for the measurement of CYP2E1 activity. CYP2E1 protein level was increased upon cultivation of cells in the presence of the solvents for 24 hr. Determination of CYP2E1 activities after 24 hr cultivation with the solvents demonstrated that acetone or dimethylsulphoxide increased, whereas pyridine inhibited the activities. This differential effect of the solvents on CYP2E1 activities persisted to subsequent 24 hr. Competitive inhibition study suggested that pyridine has stronger binding affinity to CYP2E1 than acetone or dimethylsulphoxide. These results demonstrate that different binding affinity of the solvents to CYP2E1 plays important role in determining real CYP2E1 activity in intact cells after exposure to the solvents. Present study would be helpful in precise understanding of human CYP2E1-mediated toxicity.
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