Cellular resistance to daunomycin in Chinese hamster cells in vitro.

Chinese hamster cell lines resistant to daunomycin (DM) were developed by direct exposure to the antibiotic. Increase in resistance up to 883-fold was obtained. Evaluation of dose-response data for sensitive and resistant sublines revealed complete cross-resistance to the chemically closely related antibiotic adriamycin as well as considerable cross-resistance to actinomycin D. Radioautographic experiments demonstrated that degree of resistance to DM is inversely related to degree of nuclear labeling by tritiated DM. Thus, correspondence between decreased sensitivity and decreased uptake for the DM-resistant cells, and the similarity of these results with those obtained in a previous radioautographic study of actinomycin Dand DM-resistant sublines with tritiated actinomycin D suggest that resistance to DM is due primarily to differences in the cellular membrane resulting in decreased permeability to drug.