The influence of bone marrow depletion on intestinal radiation damage

Abstract

These experiments were designed to test the hypothesis that bone marrow damage contributes to lethality when the endpoint used is LD50 for gastrointestinal damage. Specific pathogen-free mice were irradiated to the total body, total abdomen, or to the total body followed by rescue with syngeneic bone marrow cells. The relationship between animal survival and jejunal crypt survival was also examined under these three experimental conditions. The LD50/10 after total abdominal irradiation (15.6 Gy) was higher than that for total body irradiation (11.4 Gy). Rescue with syngeneic bone marrow cells after total body irradiation also increased the LD50 10 days to 14.6 Gy. The proportion of animals surviving after total body irradiation depended on the number of bone marrow cells injected as a rescue inoculum. Hence gastrointestinal death after total body irradiation is influenced by bone marrow depletion. Crypt survival, however, was similar following all three experimental procedures. These data, therefore, demonstrate a dissociation between a clonogenic and lethality assay of intestinal damage. Furthermore, a comparison of crypt survival at the LD50 under the different conditions showed that a factor of 10 times more crypts were needed to rescue a mouse from gut lethality when the total body was irradiated than when only the total abdomen was treated. Hence, the concept of the intestinal “tissue rescuing unit” as a precise and constant number of crypts is inappropriate and will vary with the experimental conditions.