title: DNA damage and nucleotide excision repair capacity in healthy individuals.
abstract: Interindividual differences in DNA repair capacity (DRC) represent an important source of variability in genome integrity and thus influence health risk. In the last decade, DRC measurement has attracted attention as a potential biomarker in cancer prediction. Aim of the present exploratory study was to characterize the variability in DNA damage and DRC on 100 healthy individuals and to identify biological, lifestyle, or genetic factors modulating these parameters. The ultimate goal was to obtain reference data from cancer-free population, which may constitute background for further investigations on cancer patients. The endogenous DNA damage was measured as a level of DNA single-strand breaks and DRC, specific for nucleotide excision repair (NER), was evaluated using modified comet assay, following the challenge of peripheral blood mononuclear cells with benzo[a]pyrene diolepoxide. Additionally, genetic polymorphisms in NER genes (XPA, XPC, XPD, and XPG) were assessed. We have observed a substantial interindividual variability for both examined parameters. DNA damage was significantly affected by gender and alcohol consumption (P = 0.003 and P = 0.012, respectively), whereas DRC was associated with family history of cancer (P = 0.012). The stratification according to common variants in NER genes showed that DNA damage was significantly modulated by the presence of the variant T allele of XPC Ala499Val polymorphism (P = 0.01), while DRC was modulated by the presence of the A allele of XPA G23A polymorphism (P = 0.048). Our results indicate the range of endogenous DNA single-strand breaks and capacity of NER in healthy volunteers as well as the role of potentially relevant confounders. Environ. Mol. Mutagen. 2011. © 2011 Wiley-Liss, Inc.
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague.
authors.forename: Jana
authors.initials: J
authors.lastname: Slyskova
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Veronika
authors.initials: V
authors.lastname: Polakova
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stetina
authors.forename: Jana
authors.initials: J
authors.lastname: Schmuczerova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Smerhovsky
authors.forename: Ludmila
authors.initials: L
authors.lastname: Lipska
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000328:Adult; D000428:Alcohol Drinking; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012737:Sex Factors
chemical_list: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide