Friedman S, Cheong L C
Biochem Pharmacol. 1984 Aug 15;33(16):2675-9. doi: 10.1016/0006-2952(84)90644-0.
5-Azacytidine inhibits Escherichia coli DNA(cytosine-5)methylase when added to growing cells. The time-course of recovery of methylase activity and the appearance of 5-methylcytosine in DNA following removal of the drug was studied. When E. coli K12 was treated with 5-azacytidine for 30 min, DNA (cytosine-5)methylase levels decreased to less than 10% of control levels and slowly recovered to control levels after seven generations of growth. 5-Methylcytosine synthesis in DNA remained at less than 10% of control levels for three generations after treatment and returned to control levels after six generations of growth. In contrast, beta-galactosidase levels in induced cells, which declined to 66% of control one generation after treatment, returned to control by the third generation of growth. The rate of induction of beta-galactosidase had returned to the control rate two generations after growth resumed. Since azacytidine-containing DNA inhibits DNA-cytosine methylases in vitro, the prolonged inhibition of cytosine methylation in E. coli K12 following treatment with the drug could be due to the persistence of the drug in DNA and thus inhibition of newly synthesized enzymes.
当添加到正在生长的细胞中时，5-氮杂胞苷会抑制大肠杆菌DNA（胞嘧啶-5）甲基化酶。研究了去除药物后甲基化酶活性恢复的时间进程以及DNA中5-甲基胞嘧啶的出现情况。当用5-氮杂胞苷处理大肠杆菌K12 30分钟时，DNA（胞嘧啶-5）甲基化酶水平降至对照水平的不到10%，并在七代生长后缓慢恢复到对照水平。处理后三代内，DNA中5-甲基胞嘧啶的合成仍保持在对照水平的不到10%，并在六代生长后恢复到对照水平。相比之下，诱导细胞中的β-半乳糖苷酶水平在处理后一代降至对照水平的66%，并在第三代生长时恢复到对照水平。恢复生长两代后，β-半乳糖苷酶的诱导速率已恢复到对照速率。由于含氮杂胞苷的DNA在体外会抑制DNA-胞嘧啶甲基化酶，用该药物处理后大肠杆菌K12中胞嘧啶甲基化的长期抑制可能是由于药物在DNA中的持续存在，从而抑制了新合成的酶。
