Exposure to ultrafine particles from ambient air and oxidative stress-induced DNA damage

Elvira Vaclavik Bräuner, Lykke Forchhammer, Peter Møller, Jacob Simonsen, Marianne Glasius, Peter Wåhlin, Ole Raaschou-Nielsen, Steffen Loft, Elvira Vaclavik Bräuner, Lykke Forchhammer, Peter Møller, Jacob Simonsen, Marianne Glasius, Peter Wåhlin, Ole Raaschou-Nielsen, Steffen Loft

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/cm(3)) or filtered air (NC 91-542/cm(3)) 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.

Figures

Figure 1
Figure 1
Daily average number concentrations and size distributions of UFPs (6–700 nm in diameter) resolved into four size modes (with median diameters 11.7, 22.6, 57.1, and 212 nm) at an urban background monitoring station in Copenhagen from 15 May 2001–31 December 2004. Abbreviations: a, size mode; d, particle diameter. Vertical lines represent the median diameters on a logarithmic scale. Curved bold line is the measured size distribution and concentration of total particle numbers; dotted lines represent the modeled sum and individual mode (11.7, 22.6, 57.1, and 212 nm) concentration and size distribution.
Figure 2
Figure 2
(A) Relationship between SBs and 24-hr average exposure in terms of NCtotal (6–700 nm). (B) Relationship between FPG sites and 24-hr average exposure in terms of NCtotal (6–700 nm). Individual exposure gradients (NCNFA/NPFA) were on average 48-fold (range, 2- to 239-fold).

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