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

先前由Sasaki等人建立的LEC大鼠。[j], 14: 4-6, 1985]表现为自发性暴发性肝炎伴严重黄疸，最后表现为肝癌。分别于肝癌发生前4周和3个月测定LEC和对照组（LEA）大鼠肝脏药物代谢酶活性。4周和3个月时，LEC大鼠肝脏细胞色素P-450含量分别为对照组（LEA）的43%和65%。4周时，LEC大鼠的环氧化水解酶和r-谷氨酰转肽酶活性分别是LEA大鼠的2.6倍和6.9倍，而谷胱甘肽S__-转移酶活性在两菌株之间无显著差异。这些结果表明，LEC大鼠的酶变化与肝细胞化学癌变中增生性灶和结节的酶变化非常相似。此外，我们讨论了LEC大鼠中这些药物代谢酶对DNA甲基化程度的可能依赖性。

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.