Drug effects on nucleic acid modification. I. A specific effect of 5-azacytidine on mammalian transfer RNA methylation invivo

Administration of the potent antineoplastic agent, 5-azacytidine (1-β-D-ribofuranosyl-4-amino-s-triazine-2(1H)-one), to mice causes a marked reduction of the 5-methylcytidine content of liver transfer RNA. This effect is dose-dependent and specific for the methylation of the 5-position of cytidine; the drug has no effect on 3-methylcytidine, 4-acetylcytidine, 5-methyluridine, dihydrouridine, pseudouridine, and modified purines. The mechanism of this effect has not yet been elucidated but probably involves the selective inhibition of 5-methylcytosine methyltransferase(s) by 5-azacytidine itself or its metabolites. The results presented show that the modified constituents of nucleic acids provide potential targets for chemotherapeutic agents.