A rapid-mix study on the effect of lipophilicity of nitroimidazoles on the radiosensitization of mammalian cells in vitro

• Published in: International journal of radiation biology and related studies in physics, chemistry and medicine Vol. 43; no. 3; p. 329
• Main Authors: Watts, M E, Hodgkiss, R J, Jones, N R, Sehmi, D S, Woodcock, M
• Format: Journal Article
• Language: English
• Published: England 1983
• Subjects: Animals; Cell Line; Cell Survival - drug effects; Cell Survival - radiation effects; Cricetinae; Dose-Response Relationship, Radiation; Misonidazole - analogs & derivatives; Misonidazole - pharmacology; Nitroimidazoles - pharmacology; Radiation-Sensitizing Agents - pharmacology
• ISSN: 0020-7616
• DOI: 10.1080/09553008314550371

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.