Intracellular Adriamycin Levels and Cytotoxicity in Adriamycin-Sensitive and Adriamycin-Resistant P388 Mouse Leukemia Cells234

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Abstract
Adriamycin (ADR) (NSC-123127) uptake and retention in ADR-sensitive P388 leukemia (P388/S) and ADR-resistant P388 leukemia (P388/R) cells were compared by fluorometry and laser flow cytometry (FCM) and were correlated with cytotoxic effects. Drug levels in P388/R cells treated in vitro with ADR (1–10 μg/ml) were twofold to fourfold lower than were levels in similarly treated P388/S cells. FCM analysis of P388/S and P388/R cells exposed in vitro to ADR showed qualitative and quantitative differences in ADR fluorescence profiles of drug-treated cells (1–5 μg/ml) but not of the isolated nuclei (0.5–10 μg/ml). Drug-induced perturbations in cell cycle traverse and chromosome aberrations were seen in P388/S but not in P388/R cells treated with 0.5–5 μg ADR/ml in vitro or 4–8 mg ADR/kg in vivo. The role of FCM in rapidly comparing and quantitating cellular ADR fluorescence profiles of ADR-sensitive and ADR-resistant tumors was demonstrated.