Monitoring the effect of anti-cancer drugs on L1210 cells by a mitochondrial probe, rhodamine-123.
The cancer chemotherapeutic agents 1-beta-D-arabinofuranosylcytosine (Ara-C), methotrexate, and 5-fluorouracil cause a rapid loss of mitochondrial Rh-123 uptake in L1210 cells, which correlates with the loss of clonogenic ability. The loss of Rh-123 uptake is irreversible and occurs prior to Trypan Blue staining. Thus, the antimetabolites, unlike freeze-thawing and detergent treatments, generally cause mitochondrial damage prior to changes in plasma membrane permeability. Since the effect of antimetabolites on Rh-123 uptake is maximal at 24 h, the Rh-123 assay may provide a rapid alternative to the clonogenic assay for monitoring the cytotoxic effects of these drugs. Our results also suggest that the inhibition or impairment of mitochondrial function may be an important step in the cytocidal and/or cytostatic action of anti-cancer drugs.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy*; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism*; D014966:Xanthenes / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D012235:Rhodamines; D014966:Xanthenes; D003561:Cytarabine; D004247:DNA; D005472:Fluorouracil; D008727:Methotrexate