Acquired Radioresistance of the Crypt Epithelium of the Duodenum

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Abstract
The different cells of the body show varying degrees of “natural” or “native” radioresistance. Any change from these levels, on the positive side, has been called acquired radioresistance. There is some evidence that the crypt epithelium of the small intestine shows such radioresistance. These cells, normally radiosensitive to x-rays (Regaud, Nogier, and Lacassagne, 1; Warren and Whipple, 2), seem to become less sensitive after repeated irradiation. Warren and Whipple (3), after irradiating the abdomens of dogs, reported: “When intervals of six days or longer supervene between x-ray doses we find little if any summation and at times even a suggestion of increased tolerance to subsequent x-ray exposures.” Friedman and Warren (4), exposing rabbits to local irradiation with repeated doses of x-rays, 400 or 500 r each, described an initial inhibition of mitosis in the cells of the intestinal epithelium, followed by its reappearance despite continued application of radiation. Observations reported by Pierce (5) on the gastrointestinal tract of mice showed that repeated small doses of total-body roentgen irradiation produced an acquired radioresistance in the cells at the base of the intestinal crypts. After four daily doses of 80 r, epithelial cell death in the crypts of the duodenum was found to be at a maximum. There was less cell death after fourteen doses than after four, and after twenty and even thirty-five doses (1,600 and 2,800 r, respectively) the crypts were similar to those in controls. This suggested the desirability of using the duodenal crypt epithelium in further tests to measure radioresistance. The studies reported here were planned to repeat the work of Pierce with more closely spaced intervals, particularly during the period of greatest sensitivity of the crypt cells, with observations of specimens a few hours following irradiation and after a longer interval to allow for recovery or further degeneration (Experiment A). The second part of the work (Experiment B) was an attempt to determine (a) against how large a dose of x-rays and (b) for how long a time the increased radioresistance would be effective. Materials and Methods As CF1 mice were substituted for the ABC mice which served as the subjects of Pierce's experiment, and as the former had been shown by survival tests to be slightly more sensitive to irradiation than the ABC strain (Sacher, 6), it was decided to use a dosage of only 60 r per day instead of 80 r. The mice were divided into twelve groups as detailed below. Experiment A: One hundred Carworth female mice weighing 15 to 20 gm. each were divided into four groups. All were maintained on a normal diet in stock cages in the laboratory for about four weeks and then transferred to small square cages, usually 12 mice to a cage. Eight of the mice were kept as untreated controls (Group 3) and the remaining 92 were exposed to roentgen radiation, 60 r daily.