Effect of verapamil on rhodamine 123 mitochondrial damage in adriamycin resistant cells.
Mitochondrial damage was found in Friend leukemia cells treated with rhodamine 123 (Rho 123). In contrast, when cells resistant to the drug were similarly treated, mitochondria were unaffected. These results correlated with higher levels of Rho 123 in sensitive as compared to resistant cells. However, when resistant cells were co-treated with verapamil, intracellular Rho 123 levels reached those of sensitive cells. At these levels mitochondrial damage and subsequent cytotoxicity in resistant cells were the same as in sensitive cells. These data suggest that differences in Rho 123 mitochondrial damage and subsequent cytotoxicity in sensitive and resistant cells result entirely from increased intracellular drug levels and not from differences in mitochondrial sensitivity or other mechanisms.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D005622:Friend murine leukemia virus; D007942:Leukemia, Experimental / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects*; D020112:Rhodamine 123; D012235:Rhodamines / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*; D014966:Xanthenes / Q000494:pharmacology*
D012235:Rhodamines; D014966:Xanthenes; D020112:Rhodamine 123; D004317:Doxorubicin; D014700:Verapamil