Effect of electron affinic hypoxic cell sensitizers on the radiolytic depletion of oxygen in mammalian cells irradiated at ultrahigh dose rates.
When CHO cells are equilibrated with a low level of oxygen (e.g. 0.4% O2) and irradiated with single 3 ns pulses of electrons, a breaking survival curve is observed. This effect is believed to be the result of radiolytic oxygen depletion and can be prevented by the presence of a relatively low concentration of hypoxic cell radiosensitizer. This prevention of the breaking survival curve has been observed for 2- and 5-nitroimidazoles, nitrofurans, and diamide. It is hypothesized that the sensitizer acts by competing with oxygen for the radiation-induced intracellular oxygen-binding species, perhaps a hydrated electron adduct, leaving oxygen free to participate in radiosensitization reactions during the lifetime of the oxygen-sensitive radiation-induced target sites for lethal damage, probably DNA radicals produced by hydroxyl radical attack. The proposed role of the sensitizer in the interference with oxygen depletion is a transient phenomenon, occurring on the microsecond to millisecond time scale.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004583:Electrons; D000860:Hypoxia / Q000503:physiopathology; D010100:Oxygen / Q000528:radiation effects*; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D010100:Oxygen