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

Brian J. Leibowitz, Liang Wei, Lin Zhang, Xiaochun Ping, Michael Epperly, Joel Greenberger, Tao Cheng and Jian Yu ()
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Brian J. Leibowitz: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute
Liang Wei: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute
Lin Zhang: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute
Xiaochun Ping: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh
Michael Epperly: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh
Joel Greenberger: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh
Tao Cheng: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh
Jian Yu: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4494

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