A rapid-mix study on the effect of lipophilicity of nitroimidazoles on the radiosensitization of mammalian cells in vitro.
A liquid flow rapid-mixing apparatus has been used to study the role of lipophilicity (octanol: water partition coefficient, P) in the sensitization of hypoxic V79 cells by nitroimidazoles. Sensitization by seven neutral 2-nitroimidazoles of similar reduction potential but widely differing partition (0.11-77) and one basic 2-nitroimidazole (pKa=8.9; p=8.5 (of free base)) was studied as a function of pre-irradiation contact time ca. 3-40 ms. With increasing P, sensitization occurs at increasingly shorter pre-irradiation contact times. The results suggest that even though factors other than passive diffusion control the sensitization observed with the base Ro 03-8799 it is able to diffuse to the target site faster than midonidazole.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D006224:Cricetinae; D004307:Dose-Response Relationship, Radiation; D008920:Misonidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008920:Misonidazole; C009997:desmethylmisonidazole; C009999:benzonidazole