title: Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice.
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.
authors.affiliation: 1] Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA [2].
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Leibowitz
authors.affiliation: 1] Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA [2].
authors.forename: Liang
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ping
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Epperly
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Greenberger
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
mesh_terms: D000005:Abdomen / Q000528:radiation effects; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011832:Radiation Injuries / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; C488588:PUMA protein, mouse; D025521:Tumor Suppressor Proteins