Effect of anthracycline analogues on the appearance of newly synthesized total RNA and messenger RNA in the cytoplasm of erythroleukemia cells.

Effects of the structural analogues, adriamycin (ADM), daunomycin (DNM), carminomycin (CMM), 4-demethoxydaunomycin (4D-DNM), pyrromycin (PYM), marcellomycin (MCM), and aclacinomycin (ACM) upon total cell RNA synthesis and the appearance of total RNA and poly(A)+-RNA in the cytoplasm of uninduced Friend erythroleukemia cells were investigated. The anthracyclines inhibited cellular RNA synthesis with IC50 values of 1-3 microM (ADM, DNM), 0.3-0.5 microM (CMM, 4D-DNM, PYM), and 0.06 microM (MCM, ACM). IC50 values for the appearance of total RNA in the cytoplasm were consistently 2-3 times lower than those for total cell RNA synthesis for each anthracycline. IC50 values for the inhibition of poly(A)+-RNA in the cytoplasm by ADM, DNM, and CMM were equivalent to those for total RNA synthesis. The values for MCM and ACM were 2-3 times higher than those for total RNA synthesis. The kinetic actions of drug-induced inhibition of poly(A)+-RNA appearance in the cytoplasm and inhibition of total RNA synthesis were equivalent for ADM, DNM and CMM, whereas the other anthracyclines showed different kinetics. These studies confirm the greater sensitivity of nucleolar RNA synthesis to Class II anthracyclines in erythroleukemia cells and suggest that inhibition of post-transcriptional events may occur in cells exposed to PYM, MCM, and ACM but at higher concentrations than are required for inhibition of RNA synthesis.