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

LEC动物模型大鼠自发性肝炎和肝癌中的肝脏药物代谢酶

基本信息

批准号：
62570131
负责人：
TOSHIHIRO SUGIYAMA
金额：
$ 0.64万
依托单位：
Osaka University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570131/
关键词：
Drug Metabolizing Enzymes Fluminant Hepatitis Spontaneous Hepatoma Cytochrome P-450 LEC Rat LECラット DNAメチル化

项目摘要

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.

Sasaki等人先前建立的LEC大鼠[Rat News Lett., 14: 4-6, 1985]的特征是表现出自发性暴发性肝炎，伴有严重黄疸，最后出现肝癌。在肝癌发病前 4 周和 3 个月时，对 LEC 和对照 (LEA) 大鼠的肝脏中的药物代谢酶活性进行了测定。 4 周和 3 个月时，LEC 大鼠肝脏的细胞色素 P-450 含量分别为对照 (LEA) 值的 43% 和 65%。 4周时LEC大鼠的环氧化物水解酶和r-谷氨酰转肽酶活性分别比LEA大鼠高2.6倍和6.9倍，而谷胱甘肽S__-转移酶活性在两种品系之间没有显着差异。这些结果表明，LEC大鼠体内的酶变化与肝细胞化学癌变中的增生灶和结节中观察到的酶变化非常相似。此外，我们还讨论了 LEC 大鼠中这些药物代谢酶对 DNA 甲基化程度的可能依赖性。