Muralidhar G, Trewyn R W
Cancer Res. 1987 May 1;47(9):2440-4.
The RNA catabolite 7-methylguanine has been shown to inhibit queuine modification of tRNA in Chinese hamster embryo cells under conditions leading to in vitro transformation. Phorbol ester tumor promoters also induce queuine hypomodification of tRNA in normal human cells, and this effect was reported to be correlated directly to the appearance of an altered (transformed) cell phenotype. Based on this common macromolecular alteration, 7-methylguanine was evaluated for its ability to enhance the chemically induced transformation of cultured cells. Two-stage initiation-promotion experiments were undertaken with Chinese hamster embryo cells in vitro to compare the effects of 7-methylguanine to known tumor promoters subsequent to initiation with 3-methylcholanthrene. 7-Methylguanine was able to increase significantly the expression of type III foci as well as anchorage-independent growth, thereby confirming that it can act as a promoting agent in vitro. Methylated guanines that do not induce queuine hypomodification of tRNA were not capable of enhancing these characteristics of in vitro transformation. The results suggest that 7-methylguanine may be a natural, endogenous promoting agent, and that changes in queuine modification of tRNA may play a fundamental role in the promotion of carcinogenesis.
在导致体外转化的条件下，RNA分解代谢物7-甲基鸟嘌呤已被证明可抑制中国仓鼠胚胎细胞中tRNA的Q修饰。佛波酯肿瘤启动剂也可诱导正常人细胞中tRNA的Q修饰不足，据报道，这种效应与改变的（转化的）细胞表型的出现直接相关。基于这种常见的大分子改变，对7-甲基鸟嘌呤增强化学诱导的培养细胞转化的能力进行了评估。在中国仓鼠胚胎细胞中进行了两阶段启动-促进实验，以比较7-甲基鸟嘌呤与已知肿瘤启动剂在经3-甲基胆蒽启动后的效果。7-甲基鸟嘌呤能够显著增加III型集落的表达以及不依赖贴壁的生长，从而证实它在体外可作为一种促进剂。不诱导tRNA的Q修饰不足的甲基化鸟嘌呤不能增强体外转化的这些特征。结果表明，7-甲基鸟嘌呤可能是一种天然的内源性促进剂，并且tRNA的Q修饰变化可能在致癌作用的促进中起基本作用。
