Morgan C J, Merrill F L, Trewyn R W
Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Cancer Res. 1996 Feb 1;56(3):594-8.
tRNA isoacceptors for aspartic acid, asparagine, histidine, and tyrosine are modified in the anticodon wobble position with the deazaguanine analogue queuine. Queuine modification is defective in many tumors and transformed cell lines, and the extent of hypomodification correlates with staging and outcome in numerous human tumors. The molecular role of queuine modification in normal cells and the mechanisms of queuine hypomodification in tumors are unknown. We have characterized nontransformed C3H10T1/2 murine fibroblasts (C3H) and their ras-transfected counterparts (RasC4) with respect to the causes and effects of queuine hypomodification. RasC4 cells are hypomodified for queuine compared with C3H cells, despite increase tRNA-guanine ribosyltansferase activity. Excess exogenous queuine can cause repletion of tRNA queuine levels in RasC4 cells. Queuine modification of both C3H and RasC4 cells can be decreased by treatment with 7-methylguanine. This treatment does not affect growth in monolayer culture but enhances anchorage-independent growth of RasC4 cells greatly. These cell lines may be useful systems for the study of queuine function in normal cells and the causes and consequences of hypomodification for queuine in tumors.
天冬氨酸、天冬酰胺、组氨酸和酪氨酸的同功tRNA在反密码子摆动位置被脱氮鸟嘌呤类似物queuine修饰。在许多肿瘤和转化细胞系中，queuine修饰存在缺陷，低修饰程度与多种人类肿瘤的分期和预后相关。queuine修饰在正常细胞中的分子作用以及肿瘤中queuine低修饰的机制尚不清楚。我们已经对未转化的C3H10T1/2小鼠成纤维细胞（C3H）及其ras转染的对应细胞（RasC4）在queuine低修饰的原因和影响方面进行了表征。与C3H细胞相比，RasC4细胞的queuine修饰不足，尽管其tRNA-鸟嘌呤核糖基转移酶活性有所增加。过量的外源性queuine可使RasC4细胞中的tRNA queuine水平恢复。用7-甲基鸟嘌呤处理可降低C3H和RasC4细胞的queuine修饰。这种处理不影响单层培养中的生长，但极大地增强了RasC4细胞的不依赖贴壁生长。这些细胞系可能是研究queuine在正常细胞中的功能以及肿瘤中queuine低修饰的原因和后果的有用系统。
