title: P53-participated cellular and molecular responses to irradiation are cell differentiation-determined in murine intestinal epithelium.
abstract: OBJECTIVE
  Cells respond differently to DNA damaging agents, which may related to cell context and differentiation status. The aim of present study was to observe the cellular and molecular responses of cells in different differentiation status to ionizing irradiation (IR).
  
  
  METHODS
  Crypt-villus unit of murine small intestine was adopted as a cell differentiation model. DNA damage responses (DDRs) of crypt and villus were observed 1-24 h after 12 Gy IR using gene expression microarray analysis, immunohistochemical staining, Western blotting and Electrophoretic Mobility Shift Assay.
  
  
  RESULTS
  Microarray analysis revealed that most differentially expressed genes were related to p53 signaling pathway in crypt 4h after IR and in both crypt and villus 24h after IR. In crypt stem cells/progenitor cells, H2AX was phosphorylated and dephosphorylated quickly, Ki67 attenuated, cell apoptosis enhanced, phosphorylated P53 increased and translocated into nuclear with the ability to bind p53-specific sequence. In upper crypt (transit amplifying cells) and crypt-villus junction, cells kept survive and proliferate as indicated by retained Ki67 expression, suppressed p53 activation, and rare apoptosis.
  
  
  CONCLUSIONS
  DDRs varied with cell differentiation status and cell function in small intestinal epithelium. P53 signaling pathway could be an important regulatory mechanism of DDRs.
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Department of Radiation Medicine, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors: Fengchao
authors: F
authors: Wang
authors: Department of Chemical Defense, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors: Jin
authors: J
authors: Cheng
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Department of Radiation Medicine, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors: Dengquan
authors: D
authors: Liu
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Department of Radiation Medicine, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors: Huiqin
authors: H
authors: Sun
authors: Department of Chemical Defense, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors: Jiqing
authors: J
authors: Zhao
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Department of Radiation Medicine, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
authors: Junping
authors: J
authors: Wang
authors: Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Room Number Y3.6006, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors: Junjie
authors: J
authors: Chen
authors: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Department of Radiation Medicine, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Electronic address: suyp2003@yahoo.com.cn.
authors: Yongping
authors: Y
authors: Su
authors: Department of Chemical Defense, School of Preventive Medicine, The Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Electronic address: zouzhmin@yahoo.com.
authors: Zhongmin
authors: Z
authors: Zou
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000528:radiation effects; D053687:Adult Stem Cells / Q000166:cytology / Q000528:radiation effects; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects*; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage; D006657:Histones / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D006657:Histones; D016159:Tumor Suppressor Protein p53; C475961:gamma-H2AX protein, mouse
keywords: Apoptosis; DNA damage response; DNA repair; Signaling pathway; Small intestine epithelium