15182193

Source:http://linkedlifedata.com/resource/pubmed/id/15182193

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0007634, umls-concept:C0022702, umls-concept:C0043240, umls-concept:C0086418, umls-concept:C0242958, umls-concept:C0374711, umls-concept:C0439596, umls-concept:C1518434, umls-concept:C1705181
pubmed:issue	23
pubmed:dateCreated	2004-6-8
pubmed:abstractText	trans-4-Hydroxynonenal (HNE) is a major peroxidation product of omega-6 polyunsaturated fatty acids. The reaction of HNE with DNA produces four diastereomeric 1,N(2)-gamma-hydroxypropano adducts of deoxyguanosine (HNE-dG); background levels of these adducts have been detected in tissues of animals and humans. There is evidence to suggest that these adducts are mutagenic and involved in liver carcinogenesis in patients with Wilson's disease and in other human cancers. Here, we present biochemical evidence that in human cell nuclear extracts the HNE-dG adducts are repaired by the nucleotide excision repair (NER) pathway. To investigate the recognition and repair of HNE-dG adducts in human cell extracts, we prepared plasmid DNA substrates modified by HNE. [(32)P]-Postlabeling/HPLC determined that the HNE-dG adduct levels were approximately 1200/10(6) dG of plasmid DNA substrate. We used this substrate in an in vitro repair-synthesis assay to study the complete repair of HNE-induced DNA adducts in cell-free extracts. We observed that nuclear extracts from HeLa cells incorporated a significant amount of alpha[(32)P]dCTP in DNA that contained HNE-dG adducts by comparison with UV-irradiated DNA as the positive control. Such repair synthesis for UV damage or HNE-dG adducts did not occur in XPA cell nuclear extracts that lack the capacity for NER. However, XPA cells complemented with XPA protein restored repair synthesis for both of these adducts. To verify that HNE-dG adducts in DNA were indeed repaired, we measured HNE-dG adducts in the post-repaired DNA substrates by the [(32)P]-postlabeling/HPLC method, showing that 50-60% of HNE-dG adducts were removed from the HeLa cell nuclear extracts after 3 h at 30 degrees C. The repair kinetics indicated that the excision rate is faster than the rate of gap-filling/DNA synthesis. Furthermore, the HNE-dG adduct isomers 2 and 4 appeared to be repaired more efficiently at early time points than isomers 1 and 3.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/CA43159, http://linkedlifedata.com/resource/pubmed/grant/P30CA17613, http://linkedlifedata.com/resource/pubmed/grant/R01 CA080917-01, http://linkedlifedata.com/resource/pubmed/grant/R01 CA113447-01A2, http://linkedlifedata.com/resource/pubmed/grant/R01 CA80917
pubmed:commentsCorrections	http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-10064851, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-10660595, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-10681431, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-10749113, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-10825130, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-11087439, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-11106660, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-11124950, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-11259420, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-11275327, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-11566294, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-12078524, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-12419825, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-12733907, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-12820894, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-12929118, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-1390626, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-1409640, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-1409645, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-14637245, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-1937131, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-1944345, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-2771659, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-3943099, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-6498804, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-7479006, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-7479621, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-7614696, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-7697716, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-8052609, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-8069852, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-8110764, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-8302827, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-8565126, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-8824513, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-8895475, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-9111054, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-9192622, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-9256505, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-9403180, http://linkedlifedata.com/resource/pubmed/commentcorrection/15182193-9736307
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/0370623
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/1,N(2)-propanodeoxyguanosine, http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxy-2-nonenal, http://linkedlifedata.com/resource/pubmed/chemical/Aldehydes, http://linkedlifedata.com/resource/pubmed/chemical/Cell Extracts, http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts, http://linkedlifedata.com/resource/pubmed/chemical/Deoxyguanosine
pubmed:status	MEDLINE
pubmed:month	Jun
pubmed:issn	0006-2960
pubmed:author	pubmed-author:AminShantuS, pubmed-author:ChoudhurySujataS, pubmed-author:ChungFung-LungFL, pubmed-author:PanJishenJ, pubmed-author:RoyRabindraR
pubmed:issnType	Print
pubmed:day	15
pubmed:volume	43
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	7514-21
pubmed:dateRevised	2010-10-4
pubmed:meshHeading	pubmed-meshheading:15182193-Aldehydes, pubmed-meshheading:15182193-Cell Extracts, pubmed-meshheading:15182193-Cell Line, pubmed-meshheading:15182193-Chromatography, High Pressure Liquid, pubmed-meshheading:15182193-DNA Adducts, pubmed-meshheading:15182193-DNA Damage, pubmed-meshheading:15182193-DNA Repair, pubmed-meshheading:15182193-Deoxyguanosine, pubmed-meshheading:15182193-HeLa Cells, pubmed-meshheading:15182193-Humans, pubmed-meshheading:15182193-Kinetics, pubmed-meshheading:15182193-Molecular Structure, pubmed-meshheading:15182193-Plasmids
pubmed:year	2004
pubmed:articleTitle	Repair kinetics of trans-4-hydroxynonenal-induced cyclic 1,N2-propanodeoxyguanine DNA adducts by human cell nuclear extracts.
pubmed:affiliation	DNA Repair Laboratory, Valhalla, New York 10595, USA.
pubmed:publicationType	Journal Article

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