Suzuki K, Sugiyama T, Ookawara T, Kurosawa T, Taniguchi N
Department of Biochemistry, Osaka University Medical School, Japan.
Biochem Int. 1991 Jan;23(1):9-14.
The 5-methylcytosine (5-mCyt) content in hepatic DNA of LEC rats was measured in order to know the mechanism by which changes in the cytochrome P-450 content and gamma-glutamyl transpeptidase activity occur. At the age of 10 or 16 weeks, there was no difference in the extent of DNA methylation as compared with that of control strain (LEA) rats. However, in the hepatoma tissues that developed later in LEC animals, the percentage of 5-mCyt in the liver of LEC rats was markedly reduced. A single i.p. dose of 5-azacytidine brought about a significant reduction of 5-mCyt content with a concomitant decrease of cytochrome P-450 and an increase in gamma-glutamyl transpeptidase activity in LEC rats, whereas no such changes occurred in the control LEA rats. These results suggest that LEC rats are highly sensitive to 5-azacytidine and that a reduction in hepatic DNA methylation may play some role in the predisposition of the rats to hepatitis or hepatoma.
为了解细胞色素P-450含量和γ-谷氨酰转肽酶活性发生变化的机制，对LEC大鼠肝脏DNA中的5-甲基胞嘧啶（5-mCyt）含量进行了测定。在10周或16周龄时，与对照品系（LEA）大鼠相比，DNA甲基化程度没有差异。然而，在LEC动物后期发生的肝癌组织中，LEC大鼠肝脏中5-mCyt的百分比明显降低。单次腹腔注射5-氮杂胞苷可使LEC大鼠的5-mCyt含量显著降低，同时细胞色素P-450减少，γ-谷氨酰转肽酶活性增加，而对照LEA大鼠未发生此类变化。这些结果表明，LEC大鼠对5-氮杂胞苷高度敏感，肝脏DNA甲基化的降低可能在大鼠易患肝炎或肝癌中起一定作用。
