Sugiyama T, Takeichi N, Kobayashi H, Yoshida M C, Sasaki M, Taniguchi N
Department of Biochemistry, Osaka University Medical School, Japan.
Carcinogenesis. 1988 Sep;9(9):1569-72. doi: 10.1093/carcin/9.9.1569.
Previously we established that 'LEC rats' have displayed spontaneous fulminant hepatitis with severe jaundice, which progressed to liver cancer, and a single autosomal recessive gene is responsible for the cause of the diseases. 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 the cytochrome P-450 content of the LEC rat livers was 43% of the control (LEA) value. At 3 months the level was 65% of the control. Epoxide hydrolase, gamma-glutamyltranspeptidase and UDP-glucuronyltransferase activities were 2.6-, 6.9- and 2.4-times higher than those in the LEA rats at 4 weeks, respectively, while glutathione S-transferase activity was not significantly different between the two strains. The enzyme changes in the LEC rats are quite similar to those observed in hyperplastic foci and nodules in chemical carcinogenesis of hepatocytes.
我们先前已确定，“LEC大鼠”会出现伴有严重黄疸的自发性暴发性肝炎，并发展为肝癌，一种常染色体隐性基因是导致这些疾病的原因。在肝癌发病前4周和3个月，对LEC大鼠和对照（LEA）大鼠肝脏中的药物代谢酶活性进行了测定。在4周时，LEC大鼠肝脏中的细胞色素P - 450含量为对照（LEA）值的43%。在3个月时，该水平为对照的65%。环氧化物水解酶、γ-谷氨酰转肽酶和UDP - 葡萄糖醛酸转移酶的活性在4周时分别比LEA大鼠高2.6倍、6.9倍和2.4倍，而两种品系之间谷胱甘肽S - 转移酶活性无显著差异。LEC大鼠中的酶变化与在肝细胞化学致癌过程中增生灶和结节中观察到的变化非常相似。
