Comparative Study on Correlation between Chemical Structure and Effect on Expression of Cytochrome P450 mRNAs in Rat among Chlorinated Ethylenes, Tetrachloroethylene, Trichloroethylene, 1, 1-Dichloroethylene

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Three polychlorinated ethylenes(CEs), tetrachloroethylene(PCE), trichloroethylene(TCE)and 1, 1-dichloroethylene(DCE), were comparatively studied for their effects on the expression of cytochrome P450(CYP) mRNA forms in the liver and lung using 7-weeks-old male Wistar rats. The animals were i.p.inoculated with 0.5 g/kg of the individual CEs and sacrificed at 6-hr intervals for 30 hr for the determination of the mRNA levels of hepatic and pulmonary CYP2B and hepatic CYP2E1.A 3.5-fold increase in the expression of hepatic CYP2B mRNA was noted transiently at 6 hr in the presence of PCE. In contrast, 1, 1-DCE was suppressive and started within 6 hr and lasted for more than 30 hr, with a trough value of 15% of the control being observed around 12 to 18 hr, while there was no marked effect observed in the case of TCE-treatment. The expression of pulmonary CYP2B mRNA was severely suppressed in the presence of 1, 1-DCE during the entire observation period as was the case with its hepatic counterpart, while the temporarily enhanced expression of mRNA at 6 hr by PCE and TCE was followed by a moderate suppression, with the trough values of ca. 80 and 65% of the control, respectively, at 18 hr. Concerning the hepatic CYP2E1, the expression of mRNA was adversely affected by all the CEs with a descending order of magnitude of 1, 1-DCE, TCE and PCE with peak inhibition values of 85%, 50% and 35%, respectively. The nonselective suppressive effect of 1, 1-DCE on the expression of divergent CYP mRNAs was well correlated with the IL-1β-dependent suppression of various types of CYP mRNA in primary cultured hepatocytes previously reported. Although PCE and TCE are under stringent legislative restriction in Japan as environmental pollutants owing to their relatively stable natures, they are less toxic in terms of the inhibition of the mRNA expression of CYP forms in acute phases than short-lived 1, 1-DCE, which is inflammatory to the host animals ; the shorter the environmental life span(l, 1-DCE > TCE > PCE), the more severe the acute toxicity.
社団法人日本薬学会の論文
2001-08-01

Comparative Study on Correlation between Chemical Structure and Effect on Expression of Cytochrome P450 mRNAs in Rat among Chlorinated Ethylenes, Tetrachloroethylene, Trichloroethylene, 1, 1-Dichloroethylene

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