title: Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA.
abstract: We analysed the associations between genetic polymorphisms in genes coding for DNA repair enzymes XPD (exon 23 A --> C, K751Q), XPG (exon 15 G --> C, D1104H), XPC (exon 15 A --> C, K939Q), XRCC1 (exon 10 G --> A, R399Q) and XRCC3 (exon 7 C --> T, T241 M) and the levels of chromosomal aberrations (CAs) and single-strand breaks (SSBs) in peripheral lymphocytes in a central European population. We also measured the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines in these individuals. An elevated frequency of CAs was observed in individuals with the XPD exon 23 A allele (AA and AC) genotypes (F = 3.6, P = 0.028, ANOVA). In multifactorial analysis of variance, the XPD exon 23 polymorphism appeared as a major factor influencing CAs (F = 4.2, P = 0.017). SSBs in DNA, on the other hand, were modulated by XPD (F = 4.3, P = 0.023), XPG (F = 4.3, P = 0.024) and XRCC1 genotypes (F = 3.0, P = 0.064). Irradiation-specific DNA repair rates (reflecting mainly base excision repair activity) were affected by XRCC1 (F = 5.9, P = 0.010) and XPC polymorphisms (F = 4.2, P = 0.046, MANOVA). Our results from this study suggest that markers of genotoxicity are associated with polymorphisms in genes encoding DNA repair enzymes.
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14200 Prague 4, Czech Republic. pvodicka@biomed.cas.cz
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stetina
authors.forename: Somali
authors.initials: S
authors.lastname: Sanyal
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
authors.forename: Vincent
authors.initials: V
authors.lastname: Haufroid
authors.forename: Maria
authors.initials: M
authors.lastname: Dusinska
authors.forename: Miroslava
authors.initials: M
authors.lastname: Kuricova
authors.forename: Maria
authors.initials: M
authors.lastname: Zamecnikova
authors.forename: Ludovit
authors.initials: L
authors.lastname: Musak
authors.forename: Jana
authors.initials: J
authors.lastname: Buchancova
authors.forename: Hannu
authors.initials: H
authors.lastname: Norppa
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Zora
authors.initials: Z
authors.lastname: Matousu
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D003062:Codon; D004249:DNA Damage / Q000235:genetics*; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004277:DNA, Single-Stranded / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009152:Mutagenicity Tests; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D003062:Codon; D004265:DNA Helicases; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C086984:XPC protein, human; C497292:ERCC2 protein, human