Time/dose relationships in abdominal irradiation: a definition of principles and experimental evaluation

We have drawn upon the work of numerous investigators to formulate a model describing the principles governing the acute response of the intestinal epithelium to cytotoxic agents. Tolerance (exposure required to kill 50 per cent of the animals) to abdomen-only irradiation was measured experimentally in the mouse using a total of 17 time/dose fractionation schedules. The principle determinants of intestinal response to fractionated radiation therapy were magnitude of each fraction and the introduction of regular recovery intervals during the course of treatment. The roles of exposure per week, exposures per day, and radiation days per week were also examined. The log-log plots of endpoint v. either number of fractions or overall treatment time yielded straight lines with slopes of 0 with 54 and 0 with 59 and y intercepts of 1,270 and 812 rets respectively. The single dose for 50 per cent acute intestinallethality (LD50/6 days) was 1,610 R. It would appear that the acute intestinal tolerance to fractionated irradiation is, in the mouse, extremely dependent upon fraction number and overall treatment time. The biological basis for intestinal tolerance to cytotoxic agents is discussed in light of the results of these studies and the model initially described.