Linked Life Data

14612962

Source:http://linkedlifedata.com/resource/pubmed/id/14612962

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-12
pubmed:abstractText
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, usually arising from a background of chronic inflammatory disease. Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine produced in response to tissue injury, endotoxin exposure or infection and TNF-alpha signalling in hepatocytes is associated with an increase in oxidative stress. DNA is vulnerable to reactive oxygen species (ROS)-induced damage, which is highly mutagenic. Cells respond to DNA damage through the stabilisation of the tumor suppressor p53, which maintains genomic fidelity through induction of a cell cycle arrest in order to allow repair or elimination of the damaged cell through apoptosis. This study was carried out to determine if TNF-alpha caused oxidative DNA damage in primary cultures of murine hepatocytes and whether any damage would result in the induction of the tumor suppressor p53 and cell-cycle arrest. Using a modified Comet assay, to measure DNA damage we have demonstrated that TNF-alpha causes the formation of 8-oxo-deoxyguanosine (8-oxodG), an established marker of oxidative DNA damage, and a lesion associated with chronic hepatitis in human livers. In addition, the increase in DNA damage did not result in p53 stabilisation and TNF-alpha caused an increase in cell-cycle progression. We believe that this study indicates a possible putative role for TNF-alpha in the early stages of malignant transformation of hepatocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1107-3756
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
889-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
TNF-alpha induced DNA damage in primary murine hepatocytes.
pubmed:affiliation
Division of Pathology, College of Medicine and Veterinary Medicine, Teviot Place, University of Edinburgh, Edinburgh EH8 9AG, Scotland, UK. n.wheelhouse@ed.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't