Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice

Nat Commun. 2014 Mar 18;5:3494. doi: 10.1038/ncomms4494.

Abstract

The role of bone marrow (BM) and BM-derived cells in radiation-induced acute gastrointestinal (GI) syndrome is controversial. Here we use bone marrow transplantation (BMT), total body irradiation (TBI) and abdominal irradiation (ABI) models to demonstrate a very limited, if any, role of BM-derived cells in acute GI injury and recovery. Compared with WT BM recipients, mice receiving BM from radiation-resistant PUMA KO mice show no protection from crypt and villus injury or recovery after 15 or 12 Gy TBI, but have a significant survival benefit at 12 Gy TBI. PUMA KO BM significantly protects donor-derived pan-intestinal haematopoietic (CD45+) and endothelial (CD105+) cells after IR. We further show that PUMA KO BM fails to enhance animal survival or crypt regeneration in radiosensitive p21 KO-recipient mice. These findings clearly separate the effects of radiation on the intestinal epithelium from those on the BM and endothelial cells in dose-dependent acute radiation toxicity.

MeSH terms

  • Abdomen / radiation effects
  • Animals
  • Apoptosis / radiation effects
  • Apoptosis Regulatory Proteins / deficiency
  • Apoptosis Regulatory Proteins / genetics
  • Bone Marrow / metabolism
  • Bone Marrow / radiation effects*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / radiation effects
  • Bone Marrow Transplantation
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / radiation effects
  • Female
  • Gastrointestinal Diseases / etiology*
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / physiopathology
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / radiation effects
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Radiation Injuries / etiology*
  • Radiation Injuries / genetics
  • Radiation Injuries / metabolism
  • Radiation Injuries / physiopathology
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / genetics
  • Whole-Body Irradiation / adverse effects*

Substances

  • Apoptosis Regulatory Proteins
  • PUMA protein, mouse
  • Tumor Suppressor Proteins