Daly N J, Julia A M, Malaise E P
Département de Radiothérapie, Centre Claudius Regaud, Toulouse, France.
Int J Radiat Biol. 1988 Oct;54(4):611-9. doi: 10.1080/09553008814552051.
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.
用单剂量的全腹照射对小鼠进行预处理，会导致2个月后给予第二次单剂量照射时，空肠隐窝的放射敏感性相对降低。高压氧（3.5巴）可使存活水平恢复到初始值，这表明在预处理过的空肠中存在辐射诱导的缺氧。然而，米索硝唑并未使预处理过的空肠隐窝增敏；它降低了正常隐窝和预处理隐窝的放射敏感性。米索硝唑的这种“矛盾”效应很可能是由于腹腔注射1mg/g体重的米索硝唑产生的急性毒性副作用，因为在注射药物后小鼠的核心体温会急剧下降。将米索硝唑处理过的动物的体温人工维持在正常水平，会产生与正常对照组和预处理对照组相似的隐窝存活水平。因此，尽管从高压氧的作用来看，预处理过的肠道存在慢性缺氧，但米索硝唑并不是研究这种组织缺氧的可靠工具。在所有使用米索硝唑的体内实验中，必须控制核心体温，以避免对实验结果产生误导性的解释。
