DNA damage and nucleotide excision repair capacity in healthy individuals

Authors

  • Jana Slyskova,

    1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague
    2. Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republic
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  • Alessio Naccarati,

    1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague
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  • Veronika Polakova,

    1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague
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  • Barbara Pardini,

    1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague
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  • Ludmila Vodickova,

    1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague
    2. Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic
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  • Rudolf Stetina,

    1. Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic
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  • Jana Schmuczerova,

    1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague
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  • Zdenek Smerhovsky,

    1. Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic
    2. Institute of Epidemiology, 2nd Medical Faculty, Charles University, Prague, Czech Republic
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  • Ludmila Lipska,

    1. Faculty Thomayer Hospital, Prague, Czech Republic
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  • Pavel Vodicka

    Corresponding author
    1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague
    • Department of Molecular Biology of Cancer, Inst Expt Med, ASCR,, Videnska 1083, 14220 Prague, Czech Republic
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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.

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