Document Detail


p53 dependence of early apoptotic and proliferative responses within the mouse intestinal epithelium following gamma-irradiation.
MedLine Citation:
PMID:  8183575     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p53 is now well characterized as a tumour suppressor gene, with loss of normal p53 function being recorded as the commonest genetic event associated with human malignancy. In particular, its involvement with tumorigenesis within the intestine is well established. Normal p53 function has been shown to be crucial for the induction of apoptosis in tumour cell lines, murine thymocytes and murine haematopoietic cells following DNA damage. To elucidate further the role of p53 in the cellular response to DNA damage we have investigated the response to gamma-irradiation of crypt cells in vivo from the small and large intestine of mice bearing a constitutive p53 deletion. Four hours after gamma-irradiation, a time point at which wild type crypt cells show abundant apoptosis, crypt cells from p53-deficient mice differed in that they were completely resistant to the induction of apoptosis. The p53 dose dependence of this phenomenon was clearly shown by the intermediate level of apoptosis observed in p53 heterozygotes. Analysis of the mitotic index and the bromodeoxyuridine labelling index showed that two other responses of wild type crypts to gamma-irradiation, namely the G2 block and the reduction in bromodeoxyuridine incorporation, were both largely intact in p53 deficient animals. These observations demonstrate that p53 function is essential for a major component of the normal response to gamma-irradiation induced DNA damage in intestinal mucosal cells, and suggest that p53 deficiency permits a population of cells bearing DNA damage to escape the normal process of deletion.
Authors:
A R Clarke; S Gledhill; M L Hooper; C C Bird; A H Wyllie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  9     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-06-14     Completed Date:  1994-06-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1767-73     Citation Subset:  IM    
Affiliation:
CRC Laboratories, Department of Pathology, University Medical School, Edinburgh, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Bromodeoxyuridine / metabolism
Cell Division
DNA Damage
Epithelial Cells
Epithelium / radiation effects
Gamma Rays
Genes, p53 / physiology*
Intestines / cytology,  radiation effects*
Mice
Chemical
Reg. No./Substance:
59-14-3/Bromodeoxyuridine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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