Linked Life Data

17875398

Source:http://linkedlifedata.com/resource/pubmed/id/17875398

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2007-12-17
pubmed:abstractText
Werner syndrome is a progeroid disorder caused by mutations of the WRN gene. The encoded WRN protein belongs to the family of RecQ helicases that plays a role in the maintenance of genomic stability. Single nucleotide polymorphisms in WRN have been associated with an increased risk for some cancers and were recently linked to benzene hematotoxicity. To further address the role of WRN in benzene toxicity, we employed RNA interference (RNAi) to silence endogenous WRN in HeLa cells and examined the susceptibility of these WRN-depleted cells to the toxic effects of the benzene metabolite hydroquinone. HeLa cells were used as the experimental model because RNAi is highly effective in this system producing almost complete depletion of the target protein. Depletion of WRN led to a decrease in cell proliferation and an enhanced susceptibility to hydroquinone cytotoxicity as revealed by an increase in necrosis. WRN-depleted HeLa cells treated with hydroquinone also displayed an increase in the amount of DNA double-strand breaks as determined by the Comet assay, and an elevated DNA damage response as indicated by the sevenfold induction of gammaH2AX and acetyl-p53 (Lys373 and Lys382) over control levels. Together, these results show that WRN plays an important role in the protection of HeLa cells against the toxicity of the benzene metabolite hydroquinone, specifically in mounting a normal DNA damage response following the induction of DNA double-strand breaks. Further studies in bone marrow-derived stem or progenitor cells are required to confirm our findings in HeLa cells and expand our ability to extrapolate the results to benzene toxicity in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
649
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-61
pubmed:meshHeading
pubmed-meshheading:17875398-Apoptosis, pubmed-meshheading:17875398-Benzene, pubmed-meshheading:17875398-Blotting, Western, pubmed-meshheading:17875398-Cell Proliferation, pubmed-meshheading:17875398-Comet Assay, pubmed-meshheading:17875398-DNA Breaks, Double-Stranded, pubmed-meshheading:17875398-DNA Damage, pubmed-meshheading:17875398-DNA Repair, pubmed-meshheading:17875398-Exodeoxyribonucleases, pubmed-meshheading:17875398-Flow Cytometry, pubmed-meshheading:17875398-HeLa Cells, pubmed-meshheading:17875398-Histones, pubmed-meshheading:17875398-Humans, pubmed-meshheading:17875398-Hydroquinones, pubmed-meshheading:17875398-RNA, Small Interfering, pubmed-meshheading:17875398-RNA Interference, pubmed-meshheading:17875398-RecQ Helicases, pubmed-meshheading:17875398-Transfection, pubmed-meshheading:17875398-Tumor Suppressor Protein p53
pubmed:year
2008
pubmed:articleTitle
Depletion of WRN enhances DNA damage in HeLa cells exposed to the benzene metabolite, hydroquinone.
pubmed:affiliation
Molecular Epidemiology and Toxicology Laboratory, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural