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

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

Author information

1
1] Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA [2].
2
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
3
Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
4
1] Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA [2] State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
5
1] Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA [2] Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

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.

PMID:
24637717
PMCID:
PMC4327858
DOI:
10.1038/ncomms4494
[Indexed for MEDLINE]
Free PMC Article

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