Comparison of the Gastrointestinal Syndrome after Total-Body or Total-Abdominal Irradiation

Abstract

In pathogen-free mice, but not standard conventionally housed laboratory rodents, two distinctly different modes of early radiation lethality can be identified by modifying the irradiation technique (total-body versus abdominal irradiation) or by therapeutic intervention such as rescue of total-body-irradiated mice with syngeneic bone marrow or spleen. While damage to the gastrointestinal tract is usually designated as the predominant cause of death occurring within 10 days of radiation exposure, it was demonstrated that damage to the hematopoietic/lymphopoietic system can result in animal lethality over the same period as the gastrointestinal syndrome and that this target cell population is more radiation-sensitive than the gastrointestinal epithelium.

PHD Inhibition Mitigates and Protects Against Radiation-Induced Gastrointestinal Toxicity via HIF2

“…To test whether the knockout of PHD proteins also protected against whole body doses of lethal radiation, we performed total body irradiation (TBI) experiments on GI-PHD1/2/3KO animals at a lethal dose of 14Gy (22). Indeed, GI-PHD1/2/3KO animals exhibited a 27% survival rate (3/11 mice, Figure 1c and table S1) at 30 days compared to a 0% survival rate in the littermate control group (0/9 mice, Figure 1c and table S1), indicating that the loss PHD proteins in the gut is sufficient to protect against radiation-induced gastrointestinal mortality from abdominal and whole body radiation.…”

Krüppel-like factor 4 is a radioprotective factor for the intestine following γ-radiation-induced gut injury in mice

“…1A). Death upon high doses of irradiation was previously described (23,26,27) and is attributed to the long-term deleterious effects of irradiation on the stem cell compartment of the intestinal epithelium because mice exposed to whole-body irradiation still die within 10 days postirradiation even after the radiation-induced hematopoietic syndrome is rescued by bone marrow transplantation (36,54).…”

“…In a murine model of ␥-radiation-induced gut injury, it has been shown that, in mice exposed to Յ8 Gy, the response is characterized by apoptosis of cells within crypt of intestinal epithelium and shortening of the villi compartment that is followed by complete recovery. At the same time radiation of Ն 12 Gy causes death within 2 wk of treatment attributable to extended damage to intestinal epithelium, especially stem cells that cannot be rescued by any treatment (23,26,36,54). Considering the high toxicity of the radiation treatment to the GI tract, studies revealing mechanisms that regulate the GI response to injury following irradiation are extremely beneficial.…”

Timing of Lethality From Gastrointestinal Syndrome in Mice Revisited

“…The categorically accepted notion that mice exposed to TAI die exclusively of the GI syndrome, because unexposed BM provides sufficient protection against the BM syndrome (5,15), also needs to be re-examined. A recent study reported that in C57Bl/6 mice receiving 17 Gy TAI, all control irradiated mice died of the GI syndrome, and the addition of basic fibroblast growth factor rescued 55% of such treated mice (see Supplemental Fig.…”