TY - JOUR
T1 - Effects of 5-fluorocytidine on mammalian transfer RNA and transfer RNA methyltransferases
AU - Lu, Lee Jane W.
AU - Wen-Cheng Tseng, Tseng
AU - Randerath, Kurt
PY - 1979
Y1 - 1979
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-2952(79)90241-7
DO - 10.1016/0006-2952(79)90241-7
M3 - Article
C2 - 371626
AN - SCOPUS:0018756741
VL - 28
SP - 489
EP - 495
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 4
ER -