Hepatic drug metabolizing enzymes in the spontaneous hepatitis and hepatoma of an animal model LEC rat

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The LEC rats previously established by Sasaki et al.[Rat News Lett., 14: 4-6, 1985] were characterized as displaying spontaneous fulminant hepatitis with severe jaundice and finally liver cancer. The activities of drug metabolizing enzymes were assayed in livers from LEC and control (LEA) rats at 4 weeks and 3 months, before the onset of liver cancer. At 4 weeks and 3 months the cytochrome P-450 content of the LEC rat livers was 43% and 65% of the control (LEA) value, respectively. epoxide hydrolase and r-glutamyltranspeptidase activities in the LEC rats were 2.6- and 6.9-times higher than those in the LEA rats at 4 weeks, respectively, while glutathione S__--transferase activities was not significantly different between the two strains. These results suggest that the enzyme changes in the LEC rats are quite similar to those observed in hyperplastic foci and nodules in chemical carcinogenesis of hepatocytes. Furthermore, we discussed a possible dependence of these drug metabolizing enzymes in the LEC rat on the degree of DNA methylation.