LATE EFFECTS OF IRRADIATION IN MOUSE JEJUNUM

The response of mouse jejunum at intervals up to 1 yr after single ''priming'' doses of X-rays was assessed by crypt survival after retreatment with single doses of X-rays and morphometric analysis of changes in the intestinal submucosa. The 1st ''priming'' dose was given as a single dose to the whole abdomen. To assess crypt survival, groups of mice were retreated to the whole body with a range of test doses 2, 6 or 12 mo. later, while other groups of mice were given only the priming doses. These data were compared to crypt survival in mice not previously irradiated. The crypt dose-survival curves in mice re-irradiated at all 3 intervals after priming irradiation were displaced to higher doses in pre-treated than in non pre-treated mice and were characterized by higher D0 [mean lethal dose] values. Misonidazole given before the test exposure reversed this effect so that the dose survival curve for crypts in pre-treated mice were superimposed on that for mice not previously irradiated, suggesting that the increase in isoeffect dose and the change in the D0 in previously exposed mice was due to crypt hypoxia. Quantification of the area of the submucosa showed that its area was increased at all 3 times after the priming doses and was a result of collagen deposition and edema. Thus, the hypoxia in the crypts was probably secondary to these changes. Deaths began at 6-7 mo. after priming irradiation and were due to intestinal obstruction and stenosis. As in other tissues, 2 phases of injury can be assayed in the intestine of experimental animals.