Lu L J, Randerath K
Cancer Res. 1980 Aug;40(8 Pt 1):2701-5.
The administration of 5-azacytidine to mice leads to a specific, rapid, time-dependent, and dose-dependent decrease of transfer RNA (tRNA) cytosine-5-methyltransferase activity of mouse liver and the synthesis of tRNA specifically lacking 5-methylcytidine. The mechanism of this enzyme deficiency was investigated. The pretreatment of mice with RNA synthesis inhibitors such as actinomycin D and D-galactosamine prevented the enzyme deficiency induced by 5-azacytidine administration. These results suggested that RNA synthesis was a prerequisite for the induction by 5-azacytidine of the enzyme inhibition in vivo. Indeed, a slowly sedimenting RNA (4 to 7S) from the livers of mice treated with 5-azacytidine, when present in an in vitro tRNA methyltransferase assay, decreased specifically the activity of tRNA cytosine-5-methyltransferase. The pretreatment of mice with actinomycin D or D-galactosamine prior to the administration of 5-azacytidine effectively prevented the formation of such inhibitory RNA in vivo as determined by an in vitro tRNA methyltransferase assay. These results indicate that the administration of 5-azacytidine to mice leads to the rapid synthesis of a low-molecular-weight RNA fraction which is capable of specifically inactivating tRNA cytosine-5-methyltransferase activity in vivo and in vitro.
给小鼠施用5-氮杂胞苷会导致小鼠肝脏中转移RNA（tRNA）胞嘧啶-5-甲基转移酶活性出现特异性、快速、时间依赖性和剂量依赖性的降低，以及特异性缺乏5-甲基胞苷的tRNA的合成。对这种酶缺乏的机制进行了研究。用放线菌素D和D-半乳糖胺等RNA合成抑制剂对小鼠进行预处理，可预防因施用5-氮杂胞苷而诱导的酶缺乏。这些结果表明，RNA合成是5-氮杂胞苷在体内诱导酶抑制的先决条件。实际上，在体外tRNA甲基转移酶测定中，来自用5-氮杂胞苷处理的小鼠肝脏的沉降缓慢的RNA（4至7S）会特异性降低tRNA胞嘧啶-5-甲基转移酶的活性。在用5-氮杂胞苷给药之前，用放线菌素D或D-半乳糖胺对小鼠进行预处理，通过体外tRNA甲基转移酶测定确定，可有效预防体内此类抑制性RNA的形成。这些结果表明，给小鼠施用5-氮杂胞苷会导致快速合成一种低分子量RNA组分，该组分能够在体内和体外特异性灭活tRNA胞嘧啶-5-甲基转移酶活性。
