Effects of 5-fluorocytidine on mammalian transfer RNA and transfer RNA methyltransferases

Effects of 5-fluorocytidine on mouse liver tRNA and mouse liver tRNA methyltransferases were investigated. tRNA isolated from drug-treated tissue was shown to contain 5-fluorocytidine and 5 fluorouridine. The amounts of all 5-substituted pyrimidine nucleosides such as 5-methylcytidine, 5-methyluridine, pseudouridine and 5,6-dihydrouridine were substantially reduced. The decreased methylation of tRNA was shown to result from decreased tRNA cytosine-5-methyltransferase and tRNA uracil-5-methyltransferase activities and capacities. Incorporation of 5-fluorouridine into tRNA, as well as the effects of 5-fluorocytidine administration on the modified uridine derivatives in tRNA, suggested the in vivo conversion of 5-fluorocytosine derivatives to 5-fluorouracil derivatives, as administration of the latter had been shown previously to cause the same effects. The inhibition of tRNA cytosine-5-methyltransferase after administration of 5-fluorocytidine resembles the effect of another cytidine analog, 5-azacytidine, which is known to cause lack of 5-methylcytidine in mouse liver tRNA and the inhibition of this particular tRNA methyltransferase.