Mechanism of adriamycin resistance in a subline of mouse lymphoblastoma L5178Y cells.

The biochemical mechanism of anthracycline resistance was studied with an adriamycin-resistant subline of mouse lymphoblastoma L5178Y cells. Both uridine and thymidine uptakes in the resistant cells were observed more resistant to adriamycin and daunorubicin than those in the parental cells. Aclacinomycin A exhibited the same degree of inhibition of nucleic acid syntheses in the sensitive cells and in the resistant cells. The resistance pattern observed by the inhibition of RNA and DNA syntheses seemed to parallel that by growth inhibition. No significant difference was demonstrated between the parental and resistant cells in the inhibition of RNA and DNA polymerase reactions with isolated nuclei. The uptake and retention of [3H]adriamycin was observed significantly less in the resistant cells than in the sensitive cells. The results suggested that the adriamycin resistance may be due to alteration of the cytoplasmic membrane and/or cytoplasm, resulting in decreased uptake and retention of the antibiotic in the resistant cells.