Flow cytometric monitoring of cellular anthracycline accumulation in murine leukemic cells.
Cellular accumulation of daunorubicin (DNR), N-trifluoroacetyl-adriamycin-14-valerate, and THP-Adriamycin (THP-ADR) in doxorubicin sensitive and resistant murine leukemic P388 cells was studied with laser excited flow cytometry. Appearance of DNR fluorescence in P388/S cells was rapid in contrast to that of P388/R cells. A comparison of P388/S and P388/R cells incubated for 20-30 min showed that DNR fluorescence in P388/R cells was one-sixth that of P388/S cells. In contrast, the difference between fluorescence value of P388/S and P388/R cells similarly incubated with N-trifluoroacetyl-adriamycin-14-valerate or THP-ADR was less than 2-fold. Chlorpromazine, verapamil, and trifluoperazine increased the cellular accumulation and cytotoxicity of DNR and THP-ADR but had no major effect on N-trifluoroacetyl-adriamycin-14-valerate fluorescence or cytotoxicity in P388/R cells. Fluorometric and soft agar assays confirmed the data on the effect of these modulators on drug accumulation obtained by the more rapid method of laser flow cytometry.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D003630:Daunorubicin / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism; D005434:Flow Cytometry; D005470:Fluorometry; D007941:Leukemia P388 / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D008991:Monitoring, Physiologic; D014268:Trifluoperazine / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D014700:Verapamil / Q000494:pharmacology
D014268:Trifluoperazine; C016163:valrubicin; D004317:Doxorubicin; D014700:Verapamil; C027260:pirarubicin; D002746:Chlorpromazine; D003630:Daunorubicin