Cytotoxicity of dual function nitrofurans in rodent and human tumor cells.
The efficacy and selective hypoxic cell cytotoxicity of four dual function nitrofurans and two nitroimidazole-aziridines was determined in human (A549, HT-29) and rodent (KHT/iv) tumor cells. All bioreductive compounds were found to be less effective at killing human than mouse tumor cells (approximately 2-6-fold). This reduced cytotoxicity in the human tumor cells occurred irrespective of the state of oxygenation. In addition, the degree of selective toxicity toward hypoxic cells or the cytotoxicity factor (CF), defined as the ratio of the surviving fraction in air to that under hypoxic conditions, was (a) greater for the nitroimidazole-aziridines than for the nitrofurans and (b) less in the human than the rodent tumor cell lines investigated. For example, CF values in A549 or HT-29 cells typically were 2-4-fold lower than those determined in KHT/iv cells. This reduction in the CF in the human cells resulted from a greater loss in the hypoxic toxicity than in the aerobic toxicity when compared with the rodent cells.
Siemann
D W
DW
Tumor Biology Division, University of Rochester Cancer Center, NY 14642.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008920:Misonidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D009581:Nitrofurans / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C049944:1-(2-nitro-1-imidazoly)-3-(2,3-dimethylaziridino)-2-propanol; D000970:Antineoplastic Agents; D001388:Aziridines; D009581:Nitrofurans; D011355:Prodrugs; D011838:Radiation-Sensitizing Agents; C073475:2,3-epoxypropyl-5-nitrofuran-2-carboxylate; C073476:N-(2,3-epoxypropyl)-3-(5-nitrofuran-2-yl)-propenamide; C066399:RB 88716; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole