Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance

doi:10.1016/j.lfs.2015.10.028

	Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance
	Zhou, Xin1,3 ; Ma, Xiaofei 1,2,3,4,5; Wang, Zhenhua1,3 ; Sun, Chao 1,3,4; Wang, Yupei 1,4,5; He, Yang 1,4,5; Zhang, Hong1,3,5
刊名	LIFE SCIENCES
	2015-12-15
卷号	143 页码:80-88
关键词	NHEJ Hyperproliferation Intestinal crypt
ISSN号	0024-3205
DOI	10.1016/j.lfs.2015.10.028
英文摘要	Aims: Radiation-induced hyperproliferation of intestinal crypts is well documented, but its potential tumorigenic effects remain elusive. Here we aim to determine the genomic surveillance process during crypt hyperproliferation, and its consequential outcome after ionizing radiation. Main methods: Crypt regeneration in the intestine was induced by a single dose of 12 Gy abdominal irradiation. gamma-H2AX, 53BP1 and DNA-PKcs were used as DNA repair surrogates to investigate the inherent ability of intestinal crypt cells to recognize and repair double-strand breaks. Ki67 staining and the 5-bromo-2'-deoxyuridine incorporation assay were used to study patterns of cell proliferation in regenerating crypts. Staining for ATM, p53, Chk1 and Chk2 was performed to study checkpoint activation and release. Apoptosis was evaluated through H&E staining and terminal deoxynucleotidyl transferase (dUTP) nick-end labeling. Key findings: The ATM-p53 pathway was immediately activated after irradiation. A second wave of DSBs in crypt cells was observed in regenerating crypts, accompanied with significantly increased chromosomal bridges. The p53-related genomic surveillance pathway was not active during the regeneration phase despite DSBs and chromosomal bridges in the cells of regenerating crypts. Non-homologous end joining (NHEJ) DSBs repair was involved in the DSBs repair process, as indicated by p-DNA-PKcs staining. Significance: Intestinal crypt cells retained hyperproliferation with inactive p53-related genomic surveillance system. NHEJ was involved in the resultant genomic instability during hyperproliferation. (C) 2015 Elsevier Inc. All rights reserved.
资助项目	Key program of the National Natural Science Foundation of China[U1432248] ; National Natural Science Foundation of China[11105203] ; National Natural Science Foundation of China[11405230]
WOS关键词	DNA-DAMAGE RESPONSE ; STEM-CELLS ; APOPTOSIS ; H2AX ; REPAIR ; FRAGMENTATION ; TUMORIGENESIS ; REQUIREMENT ; ACTIVATION ; EXPRESSION
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000366956600011
资助机构	Key program of the National Natural Science Foundation of China ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/41262]
专题	中国科学院近代物理研究所
通讯作者	Zhang, Hong
作者单位	1.Chinese Acad Sci, Inst Modern Phys, Dept Heavy Ion Radiat Med, Lanzhou 730000, Peoples R China 2.Lanzhou Univ, Sch Nucl Sci & Technol, Lanzhou 730000, Peoples R China 3.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China 4.Chinese Acad Sci, Univ Chinese Acad Sci, Beijing 10049, Peoples R China 5.Natl Lab Heavy Ion Res Facil Lanzhou, Lanzhou 730000, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Xin,Ma, Xiaofei,Wang, Zhenhua,et al. Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance[J]. LIFE SCIENCES,2015,143:80-88.
APA	Zhou, Xin.,Ma, Xiaofei.,Wang, Zhenhua.,Sun, Chao.,Wang, Yupei.,...&Zhang, Hong.(2015).Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance.LIFE SCIENCES,143,80-88.
MLA	Zhou, Xin,et al."Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance".LIFE SCIENCES 143(2015):80-88.