Robert-Gero M, Lawrence F, Vigier P
Cancer Res. 1975 Dec;35(12):3571-6.
Methioninyl adenylate is a specific and potent inhibitor of the enzyme methionyl-tRNA synthetase and, consequently, of protein biosynthesis. In cultures of chick embryo fibroblasts infected with Rous sarcoma virus, incubation for a 2-day period with 1 to 3 mM concentrations of this inhibitor, as late as 4 days after infection, irreversibly prevented subsequent formation of foci of transformed cells. Later addition could also elicit the irreversible disappearance of already existing foci, by phenotypic reversion and/or cell killing. Virus production in transformed cells and replication in newly infected cells were also inhibited but to a lesser degree. Under the same conditions, the same concentrations of methioninyl adenylate caused only a reversible growth arrest of normal cells. The selective toxicity of the inhibitor for transformed cells is not due to a greater affinity for the target enzyme, but it may be due to the fact that inhibition of protein biosynthesis is only partially reversible in these cells, whereas it is fully reversible in normal cells.
甲硫氨酰腺苷酸是甲硫氨酰 - tRNA合成酶的一种特异性强效抑制剂，因此也是蛋白质生物合成的抑制剂。在用劳氏肉瘤病毒感染的鸡胚成纤维细胞培养物中，在感染后长达4天的时间里，用1至3 mM浓度的这种抑制剂孵育2天，可不可逆地阻止随后转化细胞集落的形成。较晚添加该抑制剂也可通过表型逆转和/或细胞杀伤使已存在的集落不可逆地消失。转化细胞中的病毒产生以及新感染细胞中的病毒复制也受到抑制，但程度较小。在相同条件下，相同浓度的甲硫氨酰腺苷酸仅使正常细胞产生可逆性生长停滞。该抑制剂对转化细胞的选择性毒性并非由于对靶酶具有更高的亲和力，而是可能由于蛋白质生物合成的抑制在这些细胞中仅部分可逆，而在正常细胞中则完全可逆。
