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The effects of ethyl 4-chloro-2-methylphenoxyacetate (MCPA) and other phenoxyacid compounds on hepatic xenobiotic metabolizing enzymes were studied in male rats. These compounds were administered orally 200 mg/kg/day to the rats for 2 weeks. Both MCPA and clofibrate increased the hepatic level of cytochrome P-450. In the MCPA-treated group, the activities of aniline hydroxylase and 7-ethoxycoumarin 0-deethylase increased by 15% and 1.5-fold, respectively. The free acid form of MCPA increased these activities more potently than MCPA. Both MCPA and its free acid did not change the activity of aminopyrine N-demethylase. A marked increase in the activity of aniline hydroxylase was noted in the 2, 4-dichlorophenoxyacetic acid-treated group, whereas the aminopyrine N-demethylase activity significantly decreased in the same group. Clofibrate also increased the activities of hepatic microsomal cytochrome P-450-mediated oxidation tested, but to a lesser extent when compared with the effects of MCPA. These results indicate that MCPA may have a potent effect on the hepatic metabolizing enzymes in rats, and also that the induction of xenobiotic metabolizing enzymes may change when the chemical moiety of phenoxyacid compounds is modified.ethyl 4-chloro-2-methylphenoxyacetate ; phenoxyacid herbicides ; hepatic xenobiotic metabolism ; rat ; bile acidThe death rate for biliary tract cancer (BTC) in Japan is comparatively high in the world (Yamamoto et al. 1988a). High BTC mortality rates are concentrated in areas where rice is grown in Japan, with Niigata prefecture having the highest of all. Yamamoto et al. (1986) analyzed the ecological correlation between agricultural chemicals and standardized mortality ratios (SMRs) for BTC deaths in Japan.They found that the use of ethyl 4-chloro-2-methylphenoxyacetate (MCPA), a phenoxyacid herbicide, is significantly correlated to SMRs.

Effects of ethyl 4-chloro-2-methylphenoxyacetate (MCPA) and clofibrate on the activities of hepatic lipid metabolizing enzymes in the peroxisomal fraction from rat liver were studied, and these drugs were found to potentiate the peroxisomal enzyme activity. The results imply that MCPA affects lipid metabolism as well as clofibrate. MCPA ; peroxisomal enzyme ; rat High death rate for biliary tract cancer (BTC) is concentrated in areas where rice production is high in Japan (Yamamoto et al. 1986). Yamamoto et al. analyzed the statistical correlation between agricultural chemicals and standardized mortality ratios (SMRs) for death from BTC and found that the use of ethyl 4-chloro-2-methylphenoxyacetate (MCPA), a phenoxyacid herbicide, was significantly correlated with the SMRs. MCPA itself is not mutagenic (Moriya et al. 1983) but has co-mutagenic action (Yamamoto et al. 1988 ;Shibuya et al. 1990). MCPA has not only the inductive effect on hepatic xenobiotic metabolizing enzymes ) but also the proliferative action of hepatic peroxisome. Both the microsomal drug metabolizing system and peroxisomal fatty acid /3-oxidation are know to be concerned with the biotransformation of cholesterol into bile acids. Abnormal bile composition and metabolism may be important factors in the pathogenesis of BTC. It is possible that the change of lipid metabolism in the liver affects bile formation. These considerations led us to investigate the effect of MCPA on hepatic lipid metabolism. In this study, we examined the effect of MCPA on the activities of lipid metabolizing enzymes in the hepatic peroxisomas in rats for comparison with clofibrate (ethyl 2-(p-chlorophenoxy) isobutyrate). Clofibrate, a hypolipidemic drug, has not only the proliferative action of peroxisomes ) but also the same chlorinated phenoxyacid moiety as MCPA.MCPA was dissolved in olive oil and administered orally to Sprague Dawley-strain male rats (173-196 g) for 2 weeks at 100, 200 or 300 mg/kg/day. Clofibrate was also dissolved in the same vehicle and administered at the doses of 200 or 300 mg/kg/day in the same way.The effects of MCPA and clofibrate on body weight, liver weight, and peroxisomal