Linked Life Data

18674635

Source:http://linkedlifedata.com/resource/pubmed/id/18674635

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2008-10-20
pubmed:abstractText
The tumor suppressor, p53, plays an important role in DNA damage repair, by regulating the expression of target genes. One p53-target gene, p53R2, which encodes a subunit of ribonucleotide reductase, is activated by DNA damage. We have previously developed a genotoxicity test system, using human cell lines and a p53R2-dependent luciferase reporter gene assay. 80 chemicals have been examined with this system and 40 of 43 Ames-positive chemicals induced luciferase activity. Eight Ames-negative genotoxic chemicals also induced luciferase activity. Although this assay system could, potentially, be applied to the rapid screening of chemicals that are potentially genotoxic to humans, the ability of the assay to detect genotoxic effects was unclear. In this study, to evaluate the performance of this assay system, several different types of DNA damaging agents were screened. 27 chemicals, whose genotoxic mechanisms are well known, were screened. All genotoxic compounds, except for anti-metabolites and histone deacetylase HDAC inhibitors, showed significant luciferase activity with the following rank order of potency: topoisomerase II inhibitors, intercalaters>bleomycin>topoisomerase I inhibitors>alkylating agents=DNA cross-linking agents=polycyclic aromatic hydrocarbons>spindle poisons. This assay showed greater response to those genotoxic agents that induce DNA double strand break damage compared to those agents that cause other forms of DNA damage. DNA double strand breakage initiates genomic instability, a feature of carcinogenicity. These results indicate that this assay system could be a helpful tool for predicting chemical genotoxicity and carcinogenicity in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
656
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27-35
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
A genotoxicity test system based on p53R2 gene expression in human cells: assessment of its reactivity to various classes of genotoxic chemicals.
pubmed:affiliation
Food Safety Research Institute, Nissin Food Products Co., Ltd., 2247, Noji-Cho, Kusatsu, Shiga 525-0055, Japan. k-ono@mb1.nissinfoods.co.jp
pubmed:publicationType
Journal Article