Evidence for the lack of relationship between inhibition of nucleic acid synthesis and cytotoxicity of adriamycin

The ability of adriamycin-sensitive and -resistant Sarcoma 180 cells to incorporate thymidine and uridine into macromolecular material following exposure to this antibiotic was directly compared to the degree of cell survival by measuring in the same population precursor incorporation and cloning efficiency in soft agar after different intensities of drug exposure. The concentration and time dependence of inhibition of these processes by adriamycin were compared. No correlation between the ability to incorporate radioactive precursors into DNA and RNA and the extent of cell survival was observed except at very toxic drug concentrations. The results indicate that the extent of inhibition of precursor incorporation into DNA and RNA following drug exposure is not predictive of cell survival. This finding implies that the effect of adriamycin on nucleic acid synthesis is not directly coupled to cytotoxicity.