Oncogenic transforming potential of nitroimidazole radiosensitizers.
The oncogenic transforming potentials of a number of hypoxic cell radiosensitizers have been compared including misonidazole, SR-2508, Ro-03-8799, and RSU-1069, using the C3H 10T1/2 cell system. While the dual function bioreductive 2-nitroimidazole RSU-1069 is a particularly potent hypoxic cell radiosensitizer, both in vitro and in vivo, it is also more cytotoxic and has a considerably higher oncogenic transforming potential than the other nitroimidazoles tested. In combination with radiation, RSU-1069 produces a supra-additive transforming response in C3H 10T1/2 cells. For all the other sensitizers tested, the number of transformants produced by drug and radiation combined are simply additive. RB-6145, an analog of RSU-1069 with an equivalent sensitizing efficiency, is substantially less toxic and much less oncogenic than RSU-1069. At doses that produce similar in vitro enhancement ratios, RB-6145 is no more oncogenic than misonidazole and produces an additive transforming incidence in combination with radiation. RB-6145 appears to be a promising substitute for RSU-1069 for future clinical application(s) as a hypoxic cell sensitizer.
Hall
E J
EJ
Radiological Research Laboratory, College of Physicians & Surgeons of Columbia University, New York, NY 10032.
Hei
T K
TK
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D017341:Etanidazole; D051379:Mice; D008920:Misonidazole / Q000031:analogs & derivatives / Q000633:toxicity; D009593:Nitroimidazoles / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D017341:Etanidazole; C033815:pimonidazole; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole