No oxidative stress or DNA damage in peripheral blood mononuclear cells after exposure to particles from urban street air in overweight elderly

Jette Gjerke Hemmingsen, Kim Jantzen, Peter Møller, Steffen Loft, Jette Gjerke Hemmingsen, Kim Jantzen, Peter Møller, Steffen Loft

Abstract

Exposure to traffic-related particulate matter (PM) has been associated with increased risk of lung disease, cancer and cardiovascular disease especially in elderly and overweight subjects. The proposed mechanisms involve intracellular production of reactive oxygen species (ROS), inflammation and oxidation-induced DNA damage studied mainly in young normal-weight subjects. We performed a controlled cross-over, randomised, single-blinded, repeated-measure study where 60 healthy subjects (25 males and 35 females) with age 55-83 years and body mass index above 25 kg/m(2) were exposed for 5h to either particle-filtered or sham-filtered air from a busy street with number of concentrations and PM2.5 levels of 1800/cm(3) versus 23 000/cm(3) and 3 µg/m(3) versus 24 µg/m(3), respectively. Peripheral blood mononuclear cells (PBMCs) were collected and assayed for production of ROS with and without ex vivo exposure to nanosized carbon black as well as expression of genes related to inflammation (chemokine (C-C motif) ligand 2, interleukin-8 and tumour necrosis factor), oxidative stress response (heme oxygenase (decycling)-1) and DNA repair (oxoguanine DNA glycosylase). DNA strand breaks and oxidised purines were assayed by the alkaline comet assay. No statistically significant differences were found for any biomarker immediately after exposure to PM from urban street air although strand breaks and oxidised purines combined were significantly associated with the particle number concentration during exposure. In conclusion, 5h of controlled exposure to PM from urban traffic did not change the gene expression related to inflammation, oxidative stress or DNA repair, ROS production or oxidatively damaged DNA in PBMCs from elderly overweight human subjects.

© The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.

Figures

Figure 1.
Figure 1.
(A) Particle number concentration (PNC) and (B) PM2.5 mass (mean with SD) in the exposure chamber with and without high-efficiency particle adsorption filtration of the inlet air from an urban street.
Figure 2.
Figure 2.
Production of ROS induced by incubation with 14-nm black carbon nanoparticles (0–5 µg/ml) in PBMCs isolated from 60 overweight elderly subjects after 5-h exposure to filtered air (white) or non-filtered air (grey) from an urban street, whereas the black bars are ROS production in THP-1 assayed in parallel (positive control) with black carbon nanoparticles. The data are mean ± SEM in arbitrary units.
Figure 3.
Figure 3.
Percentage change (with 95% CI) in ROS production, DNA damage and gene expression in PBMCs from 60 overweight elderly subjects related to 5-h exposure to particles in urban street air as compared exposure to filtered air from the same site. DNA damage was assessed as SB and FPG-sensitive sites by means of the comet assay. ROS production was measured immediately after blood collection as DCFH-induced fluorescence directly (baseline) and the maximum fluorescence response above baseline induced by co-incubation with carbon black 14nm particles (CB) 0.625, 1.25, 2.5 and 5 µg/ml. Gene expression levels of CCL2, IL8, TNF, OGG1 and HMOX1 were determined by RT-PCR with 18S RNA as reference.
Figure 4.
Figure 4.
DNA damage as the sum of SB and FPG-sensitive sites in PBMCs from 60 subjects aged 55–83 years and the particle number concentration in the exposure chamber where they spend 5h prior to blood collection on two occasions: one with air filtration (700–6000/cm3) and one without filtration (10 000–35 000/cm3). There was a statistically significant association between these two variables.

References

    1. Brook R. D., Rajagopalan S., Pope C. A., III, et al. (2010) Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation, 121, 2331–2378.
    1. Dockery D. W. (2009) Health effects of particulate air pollution. Ann. Epidemiol., 19, 257–263.
    1. IARC and Monographs on the Evaluation of Carcinogenic Risk to Humans (2013) Diesel and Gasoline Engine Exhausts and Some Nitroarenes, Vol. 105 IARC, Lyon, France.
    1. Ibald-Mulli A., Wichmann H. E., Kreyling W., Peters A. (2002) Epidemiological evidence on health effects of ultrafine particles. J. Aerosol Med., 15, 189–201.
    1. Loomis D., Grosse Y., Lauby-Secretan B., et al. (2014) The carcinogenicity of outdoor air pollution. Lancet Oncol., 14, 1262–1263.
    1. Pope C. A., III, Burnett R. T., Thun M. J., Calle E. E., Krewski D., Ito K., Thurston G. D. (2002) Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. J. Am. Med. Assoc., 287, 1132–1141.
    1. Schmid O., Möller W., Semmler-Behnke M., Ferron G. A., Karg E., Lipka J., Schulz H., Kreyling W. G., Stoeger T. (2009) Dosimetry and toxicology of inhaled ultrafine particles. Biomarkers, 14(Suppl. 1), 67–73.
    1. Ghio A. J., Carraway M. S., Madden M. C. (2012) Composition of air pollution particles and oxidative stress in cells, tissues, and living systems. J. Toxicol. Environ. Health. B Crit. Rev., 15, 1–21.
    1. Langrish J. P., Bosson J., Unosson J., Muala A., Newby D. E., Mills N. L., Blomberg A., Sandström T. (2012) Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms. J. Intern. Med., 272, 224–239.
    1. Møller P., Folkmann J. K., Forchhammer L., Bräuner E. V., Danielsen P. H., Risom L., Loft S. (2008) Air pollution, oxidative damage to DNA, and carcinogenesis. Cancer Lett., 266, 84–97.
    1. Møller P., Loft S. (2010) Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution. Environ. Health Perspect., 118, 1126–1136.
    1. Moller P., Jacobsen N. R., Folkmann J. K., et al. (2010) Role of oxidative damage in toxicity of particulates. Free Radic. Res., 44, 1–46.
    1. Avogbe P. H., Ayi-Fanou L., Autrup H., Loft S., Fayomi B., Sanni A., Vinzents P., Møller P. (2005) Ultrafine particulate matter and high-level benzene urban air pollution in relation to oxidative DNA damage. Carcinogenesis, 26, 613–620.
    1. Rückerl R., Schneider A., Breitner S., Cyrys J., Peters A. (2011) Health effects of particulate air pollution: a review of epidemiological evidence. Inhal. Toxicol., 23, 555–592.
    1. Sørensen M., Schins R. P., Hertel O., Loft S. (2005) Transition metals in personal samples of PM2.5 and oxidative stress in human volunteers. Cancer Epidemiol. Biomarkers Prev., 14, 1340–1343.
    1. Vinzents P. S., Møller P., Sørensen M., Knudsen L. E., Hertel O., Jensen F. P., Schibye B., Loft S. (2005) Personal exposure to ultrafine particles and oxidative DNA damage. Environ. Health Perspect., 113, 1485–1490.
    1. Loft S., Møller P. (2006) Oxidative DNA damage and human cancer: need for cohort studies. Antioxid. Redox Signal., 8, 1021–1031.
    1. Loft S., Danielsen P., Løhr M., Jantzen K., Hemmingsen J. G., Roursgaard M., Karotki D. G., Møller P. (2012) Urinary excretion of 8-oxo-7,8-dihydroguanine as biomarker of oxidative damage to DNA. Arch. Biochem. Biophys., 518, 142–150.
    1. Risom L., Dybdahl M., Bornholdt J., Vogel U., Wallin H., Møller P., Loft S. (2003) Oxidative DNA damage and defence gene expression in the mouse lung after short-term exposure to diesel exhaust particles by inhalation. Carcinogenesis, 24, 1847–1852.
    1. Risom L., Møller P., Loft S. (2005) Oxidative stress-induced DNA damage by particulate air pollution. Mutat. Res., 592, 119–137.
    1. Hemmingsen J. G., Rissler J., Lykkesfeldt J., Sallsten G., Kristiansen J., Møller P., Loft S. (2015) Controlled exposure to particulate matter from urban street air is associated with decreased vasodilation and heart rate variability in overweight and older adults. Part. Fibre Toxicol. 12, 6.
    1. Langrish J. P., Li X., Wang S., et al. (2012) Reducing personal exposure to particulate air pollution improves cardiovascular health in patients with coronary heart disease. Environ. Health Perspect., 120, 367–372.
    1. Bräuner E. V., Forchhammer L., Møller P., Simonsen J., Glasius M., Wåhlin P., Raaschou-Nielsen O., Loft S. (2007) Exposure to ultrafine particles from ambient air and oxidative stress-induced DNA damage. Environ. Health Perspect., 115, 1177–1182.
    1. Jantzen K., Roursgaard M., Desler C., Loft S., Rasmussen L. J., Møller P. (2012) Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. Mutagenesis, 27, 693–701.
    1. Danielsen P. H., Moller P., Jensen K. A., et al. (2011) Oxidative stress, DNA damage, and inflammation induced by ambient air and wood smoke particulate matter in human A549 and THP-1 cell lines. Chem. Res. Toxicol., 24, 168–184.
    1. Cao Y., Roursgaard M., Danielsen P. H., Møller P., Loft S. (2014) Carbon black nanoparticles promote endothelial activation and lipid accumulation in macrophages independently of intracellular ROS production. PLoS One, 9, e106711.
    1. Frikke-Schmidt H., Roursgaard M., Lykkesfeldt J., Loft S., Nøjgaard J. K., Møller P. (2011) Effect of vitamin C and iron chelation on diesel exhaust particle and carbon black induced oxidative damage and cell adhesion molecule expression in human endothelial cells. Toxicol. Lett., 203, 181–189.
    1. Vesterdal L. K., Mikkelsen L., Folkmann J. K., Sheykhzade M., Cao Y., Roursgaard M., Loft S., Møller P. (2012) Carbon black nanoparticles and vascular dysfunction in cultured endothelial cells and artery segments. Toxicol. Lett., 214, 19–26.
    1. Forchhammer L., Johansson C., Loft S., et al. (2010) Variation in the measurement of DNA damage by comet assay measured by the ECVAG inter-laboratory validation trial. Mutagenesis, 25, 113–123.
    1. Forchhammer L., Møller P., Riddervold I. S., Bønløkke J., Massling A., Sigsgaard T., Loft S. (2012) Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function. Part. Fibre Toxicol., 9, 7.
    1. Hemmingsen J. G., Møller P., Nøjgaard J. K., Roursgaard M., Loft S. (2011) Oxidative stress, genotoxicity, and vascular cell adhesion molecule expression in cells exposed to particulate matter from combustion of conventional diesel and methyl ester biodiesel blends. Environ. Sci. Technol., 45, 8545–8551.
    1. Jensen A., Karottki D. G., Christensen J. M., Bønløkke J. H., Sigsgaard T., Glasius M., Loft S., Møller P. (2014) Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house. Environ. Mol. Mutagen., 55, 652–661.
    1. Rissler J., Nordin E. Z., Eriksson A. C., et al. (2014) Effective density and mixing state of aerosol particles in a near-traffic urban environment. Environ. Sci. Technol., 48, 6300–6308.
    1. Lohr M., Jensen A., Eriksen L., Gronbaek M., Loft S., Moller P. (2015) Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells. Oncotarget, 6, 2641–2653.
    1. Moller P., Hemmingsen J. G., Jensen D. M., et al. (2015) Applications of the comet assay in particle toxicology: air pollution and engineered nanomaterials exposure. Mutagenesis, 30, 67–83.
    1. Danielsen P. H., Bräuner E. V., Barregard L., Sällsten G., Wallin M., Olinski R., Rozalski R., Møller P., Loft S. (2008) Oxidatively damaged DNA and its repair after experimental exposure to wood smoke in healthy humans. Mutat. Res., 642, 37–42.
    1. Hemmingsen J.G., Møller P., Jantzen K., Jönsson B.A., Albin M., Wierzbicka A., Gudmundsson A., Loft S., Rissler J. Controlled exposure to diesel exhaust and traffic noise— effects on oxidative stress and activation in mononuclear blood cells. Mutation Res, in press.
    1. Danielsen P. H., Loft S., Møller P. (2008) DNA damage and cytotoxicity in type II lung epithelial (A549) cell cultures after exposure to diesel exhaust and urban street particles. Part. Fibre Toxicol., 5, 6.
    1. Jacobsen N. R., Møller P., Jensen K. A., Vogel U., Ladefoged O., Loft S., Wallin H. (2009) Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice. Part. Fibre Toxicol., 6, 2.
    1. Bleck B., Tse D. B., Jaspers I., Curotto de Lafaille M. A., Reibman J. (2006) Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation. J. Immunol., 176, 7431–7437.
    1. Hirota J. A., Alexis N. E., Pui M., Wong S., Fung E., Hansbro P., Knight D. A., Sin D. D., Carlsten C. (2014) PM10-stimulated airway epithelial cells activate primary human dendritic cells independent of uric acid: application of an in vitro model system exposing dendritic cells to airway epithelial cell-conditioned media. Respirology, 19, 881–890.
    1. Mendoza A., Torres-Hernandez J. A., Ault J. G., Pedersen-Lane J. H., Gao D., Lawrence D. A. (2014) Silica nanoparticles induce oxidative stress and inflammation of human peripheral blood mononuclear cells. Cell Stress Chaperones, 19, 777–790.
    1. Hanley C., Thurber A., Hanna C., Punnoose A., Zhang J., Wingett D. G. (2009) The influences of cell type and ZnO nanoparticle size on immune cell cytotoxicity and cytokine induction. Nanoscale Res. Lett., 4, 1409–1420.
    1. Bhattacharya D., Santra C. R., Ghosh A. N., Karmakar P. (2014) Differential toxicity of rod and spherical zinc oxide nanoparticles on human peripheral blood mononuclear cells. J. Biomed. Nanotechnol., 10, 707–716.
    1. Forchhammer L., Loft S., Roursgaard M., Cao Y., Riddervold I. S., Sigsgaard T., Møller P. (2012) Expression of adhesion molecules, monocyte interactions and oxidative stress in human endothelial cells exposed to wood smoke and diesel exhaust particulate matter. Toxicol. Lett., 209, 121–128.
    1. Møller P., Danielsen P., Karotki D. G., et al. (2014) Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat. Res., 762, 133–166.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner