| Effect of DNA repair gene polymorphisms on BPDE-DNA adducts in human lymphocytes. | |
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MedLine Citation:
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PMID: 12115580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine whether variations in DNA repair genes are related to host DNA damage, we investigated the association between polymorphism in the XPD gene (codon 199, 312, 751) and the XRCC1 gene (codon 194, 399) and the presence of benzo(a)pyrene diolepoxide adducts to lymphocyte DNA (BPDE-DNA) in a group of male patients with incident lung cancer, all current smokers. BPDE-DNA adducts were analyzed by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry. XPD and XRCC1 genotypes were identified by PCR-RFLP. XRCC1 and XPD genotypes did not affect the levels and proportion of detectable BPDE-DNA adducts. The patients were also genotyped for the GSTM1 polymorphism, given its role in the detoxification of BPDE. Individuals with the GSTM1 deletion had significantly higher levels of BPDE-DNA adducts when they were XPD-Asp312Asp+Lys751Lys than carriers of at least one variant allele. No such association was found with the XRCC1 genotypes. Because of the small study population (n = 60), further statistical analysis of possible gene-gene and gene-environment would not be informative. This is the first study analysing the specific BPDE-DNA adduct in vivo with regard to polymorphic repair genes (XPD, XRCC1) and xenobiotic metabolizing gene (GSTM1). Our results raise the possibility that the XPD-Asp312Asp+Lys751Lys genotype may increase BPDE-DNA damage; this effect might be evident in individuals who are especially likely to have accumulated damage, probably because of lower detoxification capacity and high environmental exposure. |
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Authors:
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Roberta Pastorelli; Annalisa Cerri; Maurizio Mezzetti; Erica Consonni; Luisa Airoldi |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 100 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-12 Completed Date: 2002-07-29 Revised Date: 2007-07-24 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 9-13 Citation Subset: IM |
Copyright Information:
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Copyright 2002 Wiley-Liss, Inc. |
Affiliation:
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Laboratory of Molecular Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. rpastorelli@marionegri.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
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metabolism* DNA Adducts / metabolism* DNA Damage* DNA Helicases* DNA Repair / genetics* DNA-Binding Proteins / genetics Gas Chromatography-Mass Spectrometry Genotype Humans Lung Neoplasms / genetics Lymphocytes / metabolism* Middle Aged Polymerase Chain Reaction Polymorphism, Genetic* Polymorphism, Restriction Fragment Length Proteins / genetics Smoking Transcription Factors* Xeroderma Pigmentosum Group D Protein |
| Chemical | |
Reg. No./Substance:
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0/DNA Adducts; 0/DNA-Binding Proteins; 0/Proteins; 0/Transcription Factors; 0/X-ray repair cross complementing protein 1; 0/benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; EC 3.6.1.-/DNA Helicases; EC 5.99.-/ERCC2 protein, human; EC 5.99.-/Xeroderma Pigmentosum Group D Protein |
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