Linked Life Data

15700305

Source:http://linkedlifedata.com/resource/pubmed/id/15700305

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-4-25
pubmed:abstractText
Acute apoptotic response to genotoxic carcinogens (AARGC) might be important for controlling the consequences of mutational load in the colon. It has been shown to occur in parallel with activation of DNA repair mechanisms. Inadequate AARGC might allow development of mutated clones with the potential to progress to cancer. In this study, we tested if p53 levels were important for AARGC in the colon and whether defective AARGC was associated with increased risk for colorectal oncogenesis. Apoptosis was measured in colonic epithelium of mice from each p53 genotype (p53-/-, p53+/-, wild-type) without and 8 hr following a single injection of azoxymethane (AOM). To determine risk for carcinogen-induced colorectal cancer (CRC), groups of mice from each p53 genotype received 3 weekly injections of AOM and colons were examined for tumour 20 weeks later. Rates of spontaneous apoptosis in colon were not affected by p53 level. However, AARGC was absent in p53-/- mice and reduced by 50% in p53+/- mice (both p < 0.01) compared to wild-type mice. AOM induced tumours in 30% of wild-type mice (average multiplicity 1.0 tumours/mouse) compared to 72% of p53+/- mice (2.0 tumours/mouse, p < 0.01) and 100% of p53-/- mice (2.8 tumours/mouse, p < 0.01). Without AOM, significantly fewer mice in all groups had tumours. Rates of apoptosis in tumours were independent of p53 status. p53 dysfunction puts intestinal epithelia at increased risk of genotoxin-induced oncogenesis due to impairment of apoptotic response mechanisms. p53 levels do not appear, however, to be important for spontaneous apoptosis in normal epithelium or apoptosis in tumours. Subsequent studies are now warranted to test the converse, namely, that enhanced apoptotic response to carcinogen reduces risk for colorectal oncogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
561-7
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Absence of acute apoptotic response to genotoxic carcinogens in p53-deficient mice is associated with increased susceptibility to azoxymethane-induced colon tumours.
pubmed:affiliation
Department of Medicine, Flinders University of South Australia, Adelaide, Australia. ying.hu@flinders.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't