Differential survival of murine small and large intestinal crypts following ionizing radiation.

Abstract

Radiation survival curves have been obtained for crypts in the small and large intestine of male BDF1 mice using the microcolony assay. Four regions of the small intestine and three regions of the large intestine were studied. One of the major objectives was to determine the optimal conditions for the microcolony assay in the large bowel. Various times post-irradiation were studied using different approaches and threshold criteria for surviving crypts. Small, but statistically significant, differences were observed along the length of the small intestine, but no differences were observed between different regions of the large intestine. There was a marked difference (p < 0.001) in the response in the large compared with the small intestine (D0 = 291 +/- 14 compared with 151 +/- 4 cGy respectively with corresponding extrapolation numbers of 18 +/- 4 and 377 +/- 65). The use of tritiated thymidine or vincristine helped in the identification of true survivors in the large bowel, but these approaches are not necessary in the small bowel. The longer the time after irradiation that the samples were fixed the easier it was to identify survivors in the colon. However, the longer the time the more animals died. The optimum compromise in these studies was to use partial-body irradiation (abdomen only) and to sample on the fifth day after irradiation. With these criteria the mid-colon survival curve had a D0 = 274 +/- 28 cGy and an extrapolation number of 22 +/- 10. The results can be considered in relation to published data on the levels of p53 and bcl-2 expression and apoptosis in murine small and large bowel.