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Northwood, United Kingdom

Adams G.E.,Cancer Research Campaign Gray Laboratory | Flockhart I.R.,Cancer Research Campaign Gray Laboratory | Smithen C.E.,Cancer Research Campaign Gray Laboratory | Smithen C.E.,Roche Holding AG | And 3 more authors.
Radiation Research | Year: 2012

Radiosensitization efficiencies for seven different 2-nitroimidazoles including Ro-07-0582 and its urinary metabolite, Ro-05-9963, and two 5-nitroimidazoles including metronidazole, have been determined in hypoxic Chinese Hamster cells, line V79-379A, X-irradiated in vitro. All the compounds were active hypoxic cell sensitizers with the enhancement ratios increasing with drug concentration. The 2-nitroimidazoles were all more efficient than the 5-nitroimidazoles. Overall, the efficiencies, defined as the concentration required to give a particular enhancement ratio, varied by a factor of about 200. Electron-affinities of the sensitizers were determined by pulse radiolysis as the one-electron reduction potentials and these correlate well with the sensitization efficiencies of the compounds. The correlation extends beyond the nitroimidazole series as is shown by data for p-nitroacetophenone, nifuroxime (a nitrofuran) and oxygen itself. The nitroimidazoles varied by a factor of 70 in their octanol/water partition coefficients, but the effect of this parameter on sensitizing efficiency is small compared with the influence of electron affinity. © 2012 by Radiation Research Society. All rights of reproduction in any form reserved. Source

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