Intracellular adriamycin levels and cytotoxicity in adriamycin-sensitive and adriamycin-resistant P388 mouse leukemia cells.
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 micrograms/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 micrograms/ml) but not of the isolated nuclei (0.5- 10 micrograms/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 micrograms 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.
D000818:Animals; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000032:analysis; D002869:Chromosome Aberrations; D004317:Doxorubicin / Q000032:analysis / Q000378:metabolism*; D004351:Drug Resistance; D005434:Flow Cytometry; D005470:Fluorometry; D007941:Leukemia P388 / Q000032:analysis / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice
D004317:Doxorubicin