Differential Recovery of Small Intestinal Segments after Partial-Body Irradiation in Non-Human Primates

Abstract

In the event of a radiological attack or accident, it is more likely that the absorbed radiation dose will be heterogeneous, rather than uniformly distributed throughout the body. This type of uneven dose distribution is known as partial-body irradiation (PBI). Partial exposure of the vital organs, specifically the highly radiosensitive intestines, may cause death, if the injury is significant and the post-exposure recovery is considerably compromised. Here we investigated the recovery rate and extent of recovery from PBI-induced intestinal damage in large animals. Rhesus macaques (Macaca mulatta) were randomly divided into four groups: sham-irradiated (0 Gy), 8 Gy PBI, 11 Gy PBI and 14 Gy PBI. A single dose of ionizing radiation was delivered in the abdominal region using a uniform bilateral anteroposterior and posteroanterior technique. Irradiated animals were scheduled for euthanasia on days 10, 28 or 60 postirradiation, and sham-irradiated animals on day 60. Intestinal structural injuries were assessed via crypt depth, villus height, and mucosal surface length in the four different intestinal regions (duodenum, proximal jejunum, distal jejunum and ileum) using H&E staining. Higher radiation doses corresponded with more injury at 10 days post-PBI and a faster recovery rate. However, at 60 days post-PBI, damage was still evident in all regions of the intestine. The proximal and distal ends (duodenum and ileum, respectively) sustained less damage and recovered more fully than the jejunum.

Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model

“…TBI with a certain portion of BM shielding (5 to 50%) has been shown to compromise the functional integrity of the intestine in NHPs [ 30 , 32 , 35 , 39 , 74 ]. Recently, we reported that PBI doses of 8, 11, and 14 Gy with 50% BM spared induced a dose-dependent increase in intestinal injury characterized by reduced villous height, crypt depth, and mucosal surface area by day 10 [ 75 ]. Studies have shown that 11 Gy PBI with 5% BM shielding in an NHP model induce maximum structural injury to the intestine by day 9 [ 38 ].…”

“…Two critical determinants of the extent of jejunal damage are apoptotic cell death and loss of crypt cell proliferation [ 77 ]. Importantly, we have shown jejunum as one of the most radiosensitive regions of the small intestine [ 75 ]. Interestingly, in this study, GT3 significantly enhanced crypt survival at day 4 post-PBI; however, the effect was lost by day 7.…”