Exposure to Ultrafine Particles from Ambient Air and Oxidative Stress–Induced DNA Damage Elvira Vaclavik Bräuner,1 Lykke Forchhammer,1 Peter Møller,1 Jacob Simonsen,1 Marianne Glasius,2* Peter Wåhlin,2 Ole Raaschou-Nielsen,3 and Steffen Loft1 1Institute of Public Health, Department of Environmental and Occupational Health, University of Copenhagen, Copenhagen, Denmark; 2Department of Atmospheric Environment, National Environmental Research Institute, Roskilde, Denmark; 3Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark Abstract Background: Particulate matter, especially ultrafine particles (UFPs) , may cause health effects through generation of oxidative stress, with resulting damage to DNA and other macromolecules. Objective: We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm. Design. Twenty-nine healthy adults participated in a randomized, two-factor cross-over study with or without biking exercise for 180 min and with exposure to particles (NC 6169-15362/cm3) or filtered air (NC 91-542/cm3) for 24 hr. Methods: The levels of DNA strand breaks (SBs) , oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) in PBMCs were measured by the Comet assay. mRNA levels of OGG1, nucleoside diphosphate linked moiety X-type motif 1 (NUDT1) , and heme oxygenase-1(HO1) were determined by real-time reverse transcriptase–polymerase chain reaction. Results: Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGG1 activity and expression of OGG1, NUDT1, and HO1 were unaltered. There was a significant dose–response relationship between NC and DNA damage, with the 57-nm mode as the major contributor to effects. Concomitant exposure to ozone, nitrogen oxides, and carbon monoxide had no influence. Conclusion: Our results indicate that UFPs, especially the 57-nm soot fraction from vehicle emissions, causes systemic oxidative stress with damage to DNA and no apparent compensatory up-regulation of DNA repair within 24 hr. Key words: air pollution, biomarkers, Comet assay, DNA repair, oxidative DNA damage, ultrafine particles. Environ Health Perspect 115:1177–1182 (2007) . doi:10.1289/ehp.9984 available via http://dx.doi.org/ [Online 27 April 2007] Address correspondence to S. Loft, Department of Environmental and Occupational Health, University of Copenhagen, Øster Farimagsgade 5, DK-1014 Copenhagen K, Denmark. Telephone: 45 3532 7649. Fax: 45 3525 7686. E-mail: s.loft@pubhealth.ku.dk *Current address: Department of Chemistry, University of Aarhus, Aarhus, Denmark. The FPG enzyme was kindly provided by A. Collins, University of Oslo, Oslo, Norway. This work was supported by the Danish National Research Councils and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility) , a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (contract no 513943) . The authors declare they have no competing financial interests. Received 13 December 2006 ; accepted 27 April 2007. The full version of this article is available for free in HTML or PDF formats. |