5-Fluorouracil modulates aminoacylation of rat liver tRNA.

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.