Vulimiri S V, Nayak R
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore.
Biochem Mol Biol Int. 1993 Dec;31(6):1121-8.
Among the different classes of RNA, the effect of 5-fluorouracil (FUra), an anticancer drug, has been studied extensively on tRNA function in E. coli, but to a limited extent in eukaryotes, with specific reference to the mammalian system. Here we compared the aminoacylation function of rat liver tRNA substituted with FUra. Three hours after a single i.p. injection of 50, 250 or 500 mg/kg body wt. of FUra, total tRNAFUra50, tRNAFUra250, and tRNAFUra500, respectively were isolated from the livers of 2-3 month old male Wistar rats. The activity of tRNAFUra was compared with normal tRNA (tRNAN) isolated from saline-treated controls. tRNAFUra50 accepted [14C]-labeled total and five individual amino acids (lysine, aspartic acid, methionine, tryptophan, and serine) at a significantly higher rate compared to tRNAN. On contrary, tRNAFUra250 & 500 displayed a dose-dependent inhibition in aminoacylation with total amino acids, lysine, and methionine. Acceptance of leucine was inhibited by tRNAFUra in a dose-dependent way. Overall, the amino acid acceptance was variable among the three populations of rat liver tRNAFUra isolated with varying doses of FUra and the possible reasons for the altered function of tRNA are discussed.
在不同种类的RNA中，抗癌药物5-氟尿嘧啶（FUra）对大肠杆菌tRNA功能的影响已得到广泛研究，但在真核生物中，特别是在哺乳动物系统中的研究程度有限。在此，我们比较了用FUra取代的大鼠肝脏tRNA的氨酰化功能。单次腹腔注射50、250或500mg/kg体重的FUra三小时后，分别从2-3月龄雄性Wistar大鼠的肝脏中分离出总tRNAFUra50、tRNAFUra250和tRNAFUra500。将tRNAFUra的活性与从盐水处理对照组分离出的正常tRNA（tRNAN）进行比较。与tRNAN相比，tRNAFUra50接受[14C]标记的总氨基酸和五种单个氨基酸（赖氨酸、天冬氨酸、蛋氨酸、色氨酸和丝氨酸）的速率显著更高。相反，tRNAFUra250和500在总氨基酸、赖氨酸和蛋氨酸的氨酰化反应中表现出剂量依赖性抑制。tRNAFUra以剂量依赖性方式抑制亮氨酸的接受。总体而言，用不同剂量FUra分离得到的大鼠肝脏tRNAFUra的三个群体之间氨基酸接受情况各不相同，并讨论了tRNA功能改变的可能原因。
