Inhibition of protein synthesis in 5-azacytidine-treated HeLa cells

Abstract

Inhibition of protein and RNA synthesis was observed in HeLa cells treated with 5-azacytidine (5-aza-C). Intracellularly, the methylation of phenol-extractable RNA (4-5S, 18S and 28S) was rapidly diminished. The bulk tRNA isolated from 5-aza-C-treated cells differed from the tRNA isolated from untreated cells in its elution on DEAE-cellulose; the difference in the mobility of the tRNA species was dependent on the dose and length of 5-aza-C treatment. The reported reduction of tRNA acceptor activity in 5-aza-C-treated cells was also observed. A simultaneous addition of cytidine or uridine could partially reverse the inhibitory effects produced by 5-aza-C. It appears that the incorporation of the phosphorylated intermediates of 5-aza-C into nucleic acids is the major cytotoxic effect of this drug.