Altered RNA/protein ratio associated with the induction of differentiation of Friend erythroleukemia cells.

The synthesis and accumulation of RNA in Friend erythroleukemia (FL) cells induced to differentiate by treatment with the aminonucleoside of puromycin (AMS) or inhibited from differentiating by the addition of inosine to the medium were studied. When FL cells were grown in the presence of AMS, RNA synthesis was substantially inhibited. This effect could not be attributed solely to the inhibition of de novo purine synthesis because the biosynthesis of purine nucleotides from labeled inosine was much less depressed. The ratios of ATP to protein and of GTP to protein were slightly modified as compared to the untreated controls. However, the RNA/protein ratio was decreased. Thus, the RNA content of the cells was reduced 30-40%, but the protein content was not significantly affected. When the cells were treated with AMS together with inosine at a concentration that inhibits AMS-induced differentiation, the RNA/protein ratio was increased as compared with that found in cells treated with AMS alone and approached the level of the ratio in untreated control cells. Adenosine had a similar effect in overcoming the inhibition of RNA synthesis by AMS. Because the RNA/protein ratio of FL cells treated with dimethyl sulfoxide or sodium butyrate, two other potent inducers, was decreased by 44%, our results suggest that a correlation exists between the RNA content of the cells and the triggering of differentiation by inducers.