Cytotoxic effect of RA233 on hypoxic B16 melanoma cells in vitro.
The pyrimido-pyrimidine derivative RA233 was found to selectively kill cultured mouse B16 melanoma cells after prolonged hypoxia. At the optimum cytotoxic concentration (100 microM), RA233 reduced cell clonogenicity by about 80% when administered during long-term hypoxia of 4 days. Comparable cytotoxicity was also evident when RA233 was present only during re-oxygenation following 4 days of hypoxia. RA233 treatment during both hypoxia and re-oxygenation resulted in the greatest cytotoxicity, with only about 1% of cells surviving such treatment. By contrast, the hypoxic cell sensitizer misonidazole was cytotoxic only when administered during hypoxia. RA233 appears to be a unique hypoxic cell sensitizer that kills long-term hypoxic tumor cells principally during re-oxygenation.
Stackpole
C W
CW
Department of Pathology, New York Medical College, Valhalla 10595.
Omar
R A
RA
Fornabaio
D M
DM
Kim
Y S
YS
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008920:Misonidazole / Q000494:pharmacology; D009012:Mopidamol / Q000494:pharmacology*; D010100:Oxygen; D011743:Pyrimidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011743:Pyrimidines; D009012:Mopidamol; D008920:Misonidazole; D010100:Oxygen