Muralidhar G, Ochieng J, Trewyn R W
Comprehensive Cancer Center, Ohio State University, Columbus, 43210.
Cancer Res. 1989 Dec 15;49(24 Pt 1):7110-4.
Altered queuine modification of tRNA has been correlated to neoplastic transformation, but no direct cause and effect relationship has been defined. In the present study, a potential role for this alteration has been assigned. The tRNA in normal Chinese hamster embryo cells is significantly more queuine modified than the tRNA in their transformed Chinese hamster embryo counterparts, even though the specific activity of the queuine modification enzyme is much lower in Chinese hamster embryo cells than in transformed Chinese hamster embryo cells. Substrate availability appears to be responsible for the queuine hypomodification of tRNA in the transformed cells, since addition of excess exogenous queuine to the culture medium results in incorporation of queuine into the anti-codon of the undermodified tRNAs. Most importantly, the excess queuine inhibits anchorage-independent growth of transformed Chinese hamster embryo cells, thereby implicating queuine hypomodification of tRNA in the expression of this transformed phenotype.
tRNA中改变的喹啉修饰已与肿瘤转化相关,但尚未确定直接的因果关系。在本研究中,已确定了这种改变的潜在作用。正常中国仓鼠胚胎细胞中的tRNA比其转化的中国仓鼠胚胎细胞中的tRNA具有明显更多的喹啉修饰,尽管喹啉修饰酶的比活性在中国仓鼠胚胎细胞中比在转化的中国仓鼠胚胎细胞中低得多。底物可用性似乎是转化细胞中tRNA喹啉修饰不足的原因,因为向培养基中添加过量的外源性喹啉会导致喹啉掺入修饰不足的tRNA的反密码子中。最重要的是,过量的喹啉抑制了转化的中国仓鼠胚胎细胞的非贴壁依赖性生长,从而表明tRNA的喹啉修饰不足与这种转化表型的表达有关。