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
N1 - Funding Information:
*This work was supported by USPHS Grants CA-1359 1 and CA-10893 (P8) and American Cancer Society Faculty Research Award PRA-108. ~Abbreviations used in the text are as foilows: mSU, methvlur~d~ne (ribothvmidine~ hU, 5.6-dihvdrourid~ne: pseudouridine; .4abu%, 3-(~-~ino-3-c~~~ypropyi)uridine; I, inosine; m ‘A, 1-methyiadenosine; mhA, No-methyladenosine; @A, ,~-[9-#-Pribofuranosyl)ptlrin-6-yi carbamoyl] threonine; m’G, l-methy~~u~osine; mlG, ~2-methylguan~ sine; m tG, ‘M2~, 2-dime~h~18u~osine; m’G, 7~methylguanosine; miC, 3-methylcytidine; mSC, 5methylcytidine; ac4C, N4-acetylcytidine; N”, a nucleoside trialcohol obtained by reduction of a nucleoside dialdehyde with sodium borohydride; 5FC, 5fluorocytosine; 5-FCR, 5-fluorocytidine; 5-FU. S-fluorouracii: S-FUR, 5.ffuorouridine; 5-azaCR, 5 azacytidine; CR, cytidine; UR, uridine; AR, adenosine; GR. auanosine: FCR-tRNA, tRNA containing 5-FCR; and mC methylase, tRNA cytosiue-5-methyitrau~ferase. Analogous abbreviations apply to other tRNA rnet~yltr~sfer~~. TCA, tr~chlor~cetic acid; and S-Ado-Met. S-adenosyl-t--methionine.
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 -