Effects of several anthracycline antitumor antibiotics on the transcriptional activity of isolated nucleoli.

The class II anthracycline antitumor antibiotics musettamycin, rudolfomycin, aclacinomycin and marcellomycin, which were shown in earlier studies to preferentially inhibit the synthesis of nucleolar RNA in intact tumor cells, were studied in an isolated nucleolar transcriptional assay. Their effects were compared with those of the nucleolar non-selective anthracyclines adriamycin, carminomycin and pyrromycin, as well as with the 10-descarbomethoxy-analogs of marcellomycin and rudolfomycin. The isolated nucleolar transcriptional assay was found to have linear activity for 30 minutes at 30 degrees C. At increasing concentrations of alpha-amanatin up to 200 micrograms/ml, the maximum degree of inhibition of transcriptional activity was found to be 6 approximately 7%. The ranking of nucleolar RNA synthesis inhibitory potencies of the class I and II anthracyclines and the 10-descarbomethoxy-analogs obtained previously in intact cells was reproduced in the isolated nucleoli assay system described here. Thus, evidence for the use of this assay as a screen for nucleolar active antitumor agents is presented.