Wagner G, Pott U, Bruckschen M, Sies H
Institut für Physiologische Chemie I, Universität Düsseldorf, Federal Republic of Germany.
Biochem J. 1988 May 1;251(3):825-9. doi: 10.1042/bj2510825.
Treatment with 5-azacytidine or dietary methyl-group deficiency effected DNA hypomethylation in mouse liver. With these treatments, NAD(P)H: quinone oxidoreductase (EC 1.6.99.2) and some glutathione S-transferase (EC 2.5.1.18) activities were over-expressed, lactate dehydrogenase (EC 1.1.1.27) activity was unaffected and the level of cytochrome P-450 was decreased. The 5-azacytidine induction of NAD(P)H: quinone oxidoreductase was significantly suppressed by puromycin, suggesting that increased enzyme activity results from an elevated level of enzyme-protein synthesis. Regulation at the transcriptional level was revealed by a substantial increase in mRNA of NAD(P)H: quinone oxidoreductase, as shown by Northern-blot analysis. The enzyme pattern observed with 5-azacytidine and with the (carcinogenic) dietary methyl-group deficiency resembles that found in hepatic nodules.
用5-氮杂胞苷治疗或饮食中甲基缺乏会导致小鼠肝脏DNA低甲基化。通过这些处理，NAD(P)H：醌氧化还原酶（EC 1.6.99.2）和一些谷胱甘肽S-转移酶（EC 2.5.1.18）的活性过度表达，乳酸脱氢酶（EC 1.1.1.27）的活性未受影响，细胞色素P-450的水平降低。嘌呤霉素可显著抑制5-氮杂胞苷对NAD(P)H：醌氧化还原酶的诱导作用，这表明酶活性的增加是由于酶蛋白合成水平的提高。Northern印迹分析显示，NAD(P)H：醌氧化还原酶的mRNA大幅增加，揭示了转录水平的调控。5-氮杂胞苷和（致癌性）饮食中甲基缺乏所观察到的酶模式类似于肝结节中的酶模式。
