Misonidazole-induced radio-resistance in normal and preirradiated jejunal mucosa

Pretreatment of mice with a single dose of whole-abdomen irradiation led to a relative decrease in radiosensitivity in jejunal crypts given a second single dose of irradiation 2 months later. Hyperbaric oxygen (3.5 bars) restored the survival level to initial values, suggesting that there was radiation-induced hypoxia in the primed jejunum. However, misonidazole did not sensitize primed jejunal crypts; it reduced the radiosensitivity of both normal and primed crypts. This 'paradoxical' effect of misonidazole could well be due to the acute toxic side-effects of 1 mg/g body weight misonidazole i.p., as there was a sharp drop in the core temperature of mice immediately after drug injection. Artificially maintaining the temperature of miso-treated animals at a normal level produced crypt survival levels similar to those of both normal controls and primed controls. Thus, although the primed gut is chronically hypoxic, as suggested by the effects of hyperbaric oxygen, misonidazole is not a reliable tool for the study of this tissue hypoxia. In all in vivo experiments with misonidazole, core temperature must be controlled in order to avoid misleading interpretations of experimental results.