Adriamycin and daunomycin caused a dose-dependent decrease in the uptake of radiolabeled adenine into cardiac myocytes in culture. These drugs inhibited adenine uptake at concentrations that result in no release of lactic acid dehydrogenase. Preincubation of the cells with daunomycin did not increase the inhibition of uptake. Moreover, daunomycin did not decrease the proportion of label incorporated into ATP-ADP or 5'-AMP even though it decreased the uptake and incorporation of adenine. Daunomycin did not alter the capacity of myocytes to synthesize 5'-AMP from adenine and PRPP when tested in cell extracts. Thus daunomycin did not have any effect on the conversion of adenine into nucleotides but had a major effect on the uptake mechanism. Daunomycin also inhibited the uptake of deoxyglucose and amino acids into cardiac myocytes at concentrations which had no effect on enzyme release. These results indicate that one of the early effects of anthracycline antitumor agents may be on the uptake of nutrients by cardiac cells. The inhibition of uptake of nutrients ultimately contributes to cell death.
