A pooled analysis of molecular epidemiological studies on modulation of DNA repair by host factors.

Alena Opattova, Sabine A.S. Langie, Mirta Milic, Andrew Collins, Asgeir Brevik, Erdem Coskun, Maria Dusinska, Isabel Gaivao, Ela Kadioglu, Blanca Laffon, Ricardo Marcos Dauder, Susana Pastor Benito, Jana Slyskova, Bozena Smolkova, Zsofia Szilagyi, Vanessa Valdiglesias, Pavel Vodicka, Katarina Volkovova, Stefano Bonassi, Roger W. L. Godschalk

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Levels of DNA damage represent the dynamics between damage formation and removal. Therefore, to better interpret human biomonitoring studies with DNA damage endpoints, an individual's ability to recognize and properly remove DNA damage should be characterized. Relatively few studies have included DNA repair as a biomarker and therefore, assembling and analyzing a pooled database of studies with data on base excision repair (BER) was one of the goals of hCOMET (EU-COST CA15132). A group of approximately 1911 individuals, was gathered from 8 laboratories which run population studies with the comet-based in vitro DNA repair assay. BER incision activity data were normalized and subsequently correlated with various host factors. BER was found to be significantly higher in women. Although it is generally accepted that age is inversely related to DNA repair, no overall effect of age was found, but sex differences were most pronounced in the oldest quartile (>61 years). No effect of smoking or occupational exposures was found. A body mass index (BMI) above 25 kg/m 2 was related to higher levels of BER. However, when BMI exceeded 35 kg/m 2, repair incision activity was significantly lower. Finally, higher BER incision activity was related to lower levels of DNA damage detected by the comet assay in combination with formamidopyrimidine DNA glycosylase (Fpg), which is in line with the fact that oxidatively damaged DNA is repaired by BER. These data indicate that BER plays a role in modulating the steady-state level of DNA damage that is detected in molecular epidemiological studies and should therefore be considered as a parallel endpoint in future studies.

Original languageEnglish
Article number503447
Pages (from-to)503447
Number of pages7
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume876-877
DOIs
Publication statusPublished - 1 Apr 2022

Keywords

  • BMI
  • Base excision repair
  • Biomarker
  • Comet assay
  • DNA repair
  • Oxidatively damaged DNA

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