Hydroxyl-radical-dependent DNA damage by ambient particulate matter from contrasting sampling locations.

Exposure to ambient particulate matter (PM) has been reported to be associated with increased respiratory, cardiovascular, and malignant lung disease. Previously we have shown that PM can induce oxidative DNA damage in A549 human lung epithelial cells. The aims of the present study were to investigate the variability of the DNA-damaging properties of PM sampled at different locations and times and to relate the observed effects to the hydroxyl-radical (OH)-generating activities of these samples. Weekly samples of coarse (10-2.5 microm) and fine (<2.5 microm) PM from four sites (Nordrheim Westfalen, Germany) were analyzed for hydrogen-peroxide-dependent OH formation using electron paramagnetic resonance and formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf thymus DNA using an immuno-dot-blot assay. DNA strand breakage by fine PM in A549 human lung epithelial cells was quantified using the alkaline comet assay. Both PM size distribution fractions elicited OH generation and 8-OHdG formations in calf thymus DNA. Significantly higher OH generation was observed for PM sampled at urban/industrial locations and for coarse PM. Samples of fine PM also caused DNA strand breakage in A549 cells and this damage could be prevented using the hydroxyl-radical scavengers 5,5-dimethyl-1-pyrroline-N-oxide and dimethyl sulfoxide. The observed DNA strand breakage appeared to correlate with the hydroxyl-radical-generating capacities of the PM samples but with different profiles for rural versus urban/industrial samples. In conclusion, when considered at equal mass, OH formation of PM shows considerable variability with regard to the sampling location and time and is correlated with its ability to cause DNA damage.

[1]  Ning Li,et al.  USE OF A STRATIFIED OXIDATIVE STRESS MODEL TO STUDY THE BIOLOGICAL EFFECTS OF AMBIENT CONCENTRATED AND DIESEL EXHAUST PARTICULATE MATTER , 2002, Inhalation toxicology.

[2]  R. Burnett,et al.  Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. , 2002, JAMA.

[3]  P. Borm,et al.  Ambient exposure and nasal inflammation in adults and children--a preliminary analysis. , 2002, International journal of hygiene and environmental health.

[4]  W. Pryor,et al.  Role of free radicals in the toxicity of airborne fine particulate matter. , 2001, Chemical research in toxicology.

[5]  Steffen Loft,et al.  Personal exposure to PM2.5 and biomarkers of DNA damage. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[6]  A. Collins,et al.  Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. , 1993, Carcinogenesis.

[7]  P. Borm,et al.  Ambient Particulate Matter Induces Oxidative Dna Damage in Lung Epithelial Cells , 2000, Inhalation toxicology.

[8]  J. Carter,et al.  Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. , 1997, Toxicology and applied pharmacology.

[9]  David M. Brown,et al.  Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. , 2001, Toxicology and applied pharmacology.

[10]  R. Devlin,et al.  Inflammatory lung injury after bronchial instillation of air pollution particles. , 2001, American journal of respiratory and critical care medicine.

[11]  Tingming Shi,et al.  Soluble metals as well as the insoluble particle fraction are involved in cellular DNA damage induced by particulate matter , 2004, Molecular and Cellular Biochemistry.

[12]  Thomas Kuhlbusch,et al.  Hydroxyl radical generation by electron paramagnetic resonance as a new method to monitor ambient particulate matter composition. , 2003, Journal of environmental monitoring : JEM.

[13]  K. Dreher,et al.  Particulate Matter Physicochemistry and Toxicology: In Search of Causality—A Critical Perspective , 2000, Inhalation toxicology.

[14]  R. Tice,et al.  Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing , 2000, Environmental and molecular mutagenesis.

[15]  J Schwartz,et al.  Confounding and Effect Modification in the Short-Term Effects of Ambient Particles on Total Mortality: Results from 29 European Cities within the APHEA2 Project , 2001, Epidemiology.

[16]  L. Verschaeve,et al.  Genotoxicity of PM10 and extracted organics collected in an industrial, urban and rural area in Flanders, Belgium. , 2004, Environmental research.

[17]  S L Zeger,et al.  Estimating particulate matter-mortality dose-response curves and threshold levels: an analysis of daily time-series for the 20 largest US cities. , 2000, American journal of epidemiology.

[18]  J. Musarrat,et al.  Quantitative immunoanalysis of promutagenic 8-hydroxy-2'-deoxyguanosine in oxidized DNA. , 1994, Carcinogenesis.

[19]  J Inmon,et al.  Air pollution particles mediated oxidative DNA base damage in a cell free system and in human airway epithelial cells in relation to particulate metal content and bioreactivity. , 2001, Chemical research in toxicology.

[20]  Vicki Stone,et al.  Inflammatory effects of coarse and fine particulate matter in relation to chemical and biological constituents. , 2004, Toxicology and applied pharmacology.

[21]  Kevin R. Smith,et al.  Particle characteristics responsible for effects on human lung epithelial cells. , 2002, Research report.

[22]  H. Ochi,et al.  Quantitative immunohistochemical determination of 8-hydroxy-2'-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[23]  J. Carter,et al.  Respiratory epithelial cells demonstrate lactoferrin receptors that increase after metal exposure. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[24]  P. Borm,et al.  Oxidative DNA damage in peripheral blood lymphocytes of coal workers , 1995, International archives of occupational and environmental health.

[25]  Guoping Wu,et al.  Children's respiratory morbidity prevalence in relation to air pollution in four Chinese cities. , 2002, Environmental health perspectives.

[26]  H. Kasai,et al.  Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues , 1987, Nature.

[27]  Vicki Stone,et al.  Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10). , 2003, Free radical biology & medicine.

[28]  P. Borm,et al.  Temporal variation of hydroxyl radical generation and 8-hydroxy-2′-deoxyguanosine formation by coarse and fine particulate matter , 2003, Occupational and environmental medicine.

[29]  W. MacNee,et al.  Free radical activity of PM10: iron-mediated generation of hydroxyl radicals. , 1997, Environmental health perspectives.

[30]  L. Verschaeve,et al.  Genotoxic effects of carbon black particles, diesel exhaust particles, and urban air particulates and their extracts on a human alveolar epithelial cell line (A549) and a human monocytic cell line (THP‐1) , 2001, Environmental and molecular mutagenesis.

[31]  A. Ghio,et al.  EFFECT OF METAL REMOVAL ON THE TOXICITY OF AIRBORNE PARTICULATE MATTER FROM THE UTAH VALLEY , 2002, Inhalation toxicology.

[32]  Joachim Heinrich,et al.  Metal-rich ambient particles (particulate matter 2.5) cause airway inflammation in healthy subjects. , 2004, American journal of respiratory and critical care medicine.

[33]  A. Nel,et al.  The role of particulate pollutants in pulmonary inflammation and asthma: evidence for the involvement of organic chemicals and oxidative stress , 2001, Current opinion in pulmonary medicine.

[34]  L. Marnett,et al.  Oxyradicals and DNA damage. , 2000, Carcinogenesis.

[35]  P. Borm,et al.  Oxidant-induced DNA damage by quartz in alveolar epithelial cells. , 2002, Mutation research.