Ambient Particulate Air Pollution Research Articles

Short-Term Effects of Air Pollution on Exhaled Nitric Oxide in Diabetic Patients

ISEE-0328 Background and Objective: Ambient particulate air pollution has been associated with biomarkers of pulmonary and systemic inflammation. In this study we examine if ambient particle levels are associated with exhaled nitric oxide (NO), a marker for pulmonary inflammation, in a sample of subjects with type 2 diabetes from the Boston Metropolitan area. Methods: This analysis is based on data from the first 37 participants who completed an ongoing repeated measures study that started in September 2006. Breath samples were collected during bi-weekly clinic visits. Hourly fine particulate matter (PM2.5), sulfate (SO42-), Black Carbon (BC), and gases were measured at a central ambient monitoring station. Linear mixed models were used to examine the effects of an interquartile increase in air pollution on exhaled NO. The models contained random subject effects, fixed effects of gender, season, NO room air, and ambient pollution, and a first-order auto-regressive term. Results: The number of visits per subject ranged from two to five, with a total of 170 exhaled NO measurements. Ambient particle levels on the days preceding the clinic visit were consistently associated with levels of exhaled NO. A 4.1 μg/m3 increase in mean 48-hour PM2.5 level was associated with an increase of 0.87 ppb (0.19 to 1.56), and a 1.8 μg/m3 increase in mean 48-hour sulfate level was associated with an increase of 0.98 ppb (0.11 to 1.84) in exhaled NO. Associations with black carbon were similar. We found no associations between exhaled NO and ambient gases. Conclusion: These results suggest that in this population of diabetic subjects increased ambient levels of particulate air pollution are associated with changes in airway inflammatory status as measured by exhaled NO. This work is supported by funding from the NIEHS (ES-09825, RD-83241601).

Acute Platelet Responses to Ambient Particulate Matter

ISEE-0758 Background and Objective: Increases in ambient particulate air pollution (PM) have been associated with acute cardiovascular events over the following few hours and days in epidemiologic studies. Within 1–2 hours of intratracheal instillation of ultrafine PM, acute prothrombotic changes indicative of platelet activation have been corroborated in rodent models. We hypothesized that inhalation of ambient fine PM (PM2.5) leads to increases in platelet activation over the next few hours and days. Methods: We measured blood platelet surface activation markers in 37 healthy human subjects during 1–3 clinic visits per subject, 1 week apart (n = 85 measurements). Specific monoclonal antibodies (PAC1, CD62p, CD42b, and CD36) and flow cytometry were used to determine the mean fluorescence (MF) of each of four platelet surface markers. Using mixed regression models, we estimated the change in MF of each platelet marker associated with ambient PM2.5 concentration in the previous 24 hours, as well as moving averages out to 144 hours. Results: Each 7.56 μg/m3 increase in PM2.5 concentration in the 24 hours before the clinic visit was associated with a significant 0.34 unit (95% CI = 0.00, 0.68) increase in PAC1 and 2.45 unit (95% CI = 0.16, 4.75) increase in CD42b, with similar size changes related to PM2.5 over the previous 48 hours. Estimated PAC1 and CD42b changes for the longer moving averages were smaller and non-significant. Nonwhites had an approximately 50% greater PAC1 change than whites, but there was no difference by gender. We observed no association between CD62p or CD36 and PM2.5. Conclusion: These data suggest an acute platelet response to increases in ambient PM2.5 concentration. Further analyses will examine effect modification by specific genetic factors and specific periods of the day (e.g. rush hour), and examine whether PM2.5 effects are more acute than 24 hours.

Zinc transport by respiratory epithelial cells and interaction with iron homeostasis

Despite recurrent exposure to zinc through inhalation of ambient air pollution particles, relatively little information is known about the homeostasis of this metal in respiratory epithelial cells. We describe zinc uptake and release by respiratory epithelial cells and test the postulate that Zn(2+) transport interacts with iron homeostasis in these same cells. Zn(2+) uptake after 4 and 8 h of exposure to zinc sulfate was concentration- and time-dependent. A majority of Zn(2+) release occurred in the 4 h immediately following cell exposure to ZnSO(4). Regarding metal importers, mRNA for Zip1 and Zip2 showed no change after respiratory epithelial cell exposure to zinc while mRNA for divalent metal transporter (DMT)1 increased. Western blot assay for DMT1 protein supported an elevated expression of this transport protein following zinc exposure. RT-PCR confirmed mRNA for the metal exporters ZnT1 and ZnT4 with the former increasing after ZnSO(4). Cell concentrations of ferritin increased with zinc exposure while oxidative stress, measured as lipid peroxides, was decreased supporting an anti-oxidant function for Zn(2+). Increased DMT1 expression, following pre-incubations of respiratory epithelial cells with TNF-alpha, IFN-gamma, and endotoxin, was associated with significantly decreased intracellular zinc transport. Finally, incubations of respiratory epithelial cells with both zinc sulfate and ferric ammonium citrate resulted in elevated intracellular concentrations of both metals. We conclude that exposure to zinc increases iron uptake by respiratory epithelial cells. Elevations in cell iron can possibly affect an increased expression of DMT1 and ferritin which function to diminish oxidative stress. Comparable to other metal exposures, changes in iron homeostasis may contribute to the biological effects of zinc in specific cells and tissues.

Heart rate variability, ambient particulate matter air pollution, and glucose homeostasis: the environmental epidemiology of arrhythmogenesis in the women's health initiative.

Metabolic neuropathophysiology underlying the prediabetic state may confer susceptibility to the adverse health effects of ambient particulate matter <10 microm in diameter (PM(10)). The authors therefore examined whether impaired glucose homeostasis modifies the effect of PM(10) on heart rate variability in a stratified, random sample of 4,295 Women's Health Initiative clinical trial participants, among whom electrocardiograms and fasting blood draws were repeated at 3-year intervals from 1993 to 2004. In multilevel, mixed models weighted for sampling design and adjusted for clinical and environmental covariables, PM(10) exposure was inversely associated with heart rate variability. Inverse PM(10)-heart rate variability associations were strongest for the root mean square of successive differences in normal-to-normal RR intervals (RMSSD). Among participants with impaired fasting glucose, there were -8.3% (95% confidence interval: -13.9, -2.4) versus -0.6% (95% confidence interval: -2.4, 1.3), -8.4% (95% confidence interval: -13.8, -2.7) versus -0.3% (95% confidence interval: -2.1, 1.6), and -4.3% (95% confidence interval: -9.4, 1.0) versus -0.8% (95% confidence interval: -2.7, 1.0) decreases in the RMSSD per 10-microg/m(3) increase in PM(10) at high versus low levels of insulin (P < 0.01), insulin resistance (P < 0.01), and glucose (P = 0.16), respectively. These associations were stronger among participants with diabetes and weaker among those without diabetes or impaired fasting glucose. The findings suggest that insulin and insulin resistance exacerbate the adverse effect of PM(10) on cardiac autonomic control and thus risk of coronary heart disease among nondiabetic, postmenopausal women with impaired fasting glucose.

Could Dirty Air Cause Diabetes?

Diabetes is a growing epidemic, and it has become arguably one of the biggest health challenges of our time. Currently, more than 23 million Americans have diabetes, and the Centers for Disease Control and Prevention estimate that in the last 15 years, the number of people in the United States with diabetes has more than doubled. Diabetes is increasing at an alarming rate in Europe as well, and it is fast becoming a major health threat in developing countries such as India and China. Despite its high prevalence, however, diabetes remains somewhat of a mystery. Although type 1 diabetes mellitus could be attributed to insufficient insulin release by the β-cells of the pancreas, the origins of type 2 diabetes mellitus (which accounts for >90% of the cases of diabetes) remain obscure. Insulin resistance is a cardinal feature of type 2 diabetes mellitus; however, it is not clear how whole-body insulin resistance develops, which specific tissues are affected first and which ones later, and how metabolic changes in individual tissues contribute to the overall development of the disease and its many secondary complications. Article p 538 The origin of diabetes is equally complex. Although diabetes develops in genetically susceptible individuals, it is a complex trait and does not show simple mendelian inheritance. Because the rates of diabetes change with the environment in several population groups, it has been suggested that modifiable environmental factors and lifestyle choices account for more than 90% of adult-onset diabetes.1 Nevertheless, our understanding of the environmental causes of diabetes has remained rather rudimentary, being limited mostly to the impact of physical inactivity or unhealthy dietary choices. In this context, the study by Sun and coworkers published in the present issue of Circulation 2 is interesting because it provides new evidence showing that exposure to particulate air …

Ambient Air Pollution and Daily Mortality Among Survivors of Myocardial Infarction

Certain subgroups in the general population, such as persons with existing cardiovascular or respiratory disease, may be more likely to experience adverse health effects from air pollution. In this European multicenter study, 25,006 myocardial infarction (MI) survivors in 5 cities were recruited from 1992 to 2002 via registers, and daily mortality was followed for 6 to 12 years in relation to ambient particulate and gaseous air pollution exposure. Daily air pollution levels were obtained from central monitor sites, and particle number concentrations were measured in 2001 and estimated retrospectively based on measured pollutants and meteorology. City-specific effect estimates from time-series analyses with Poisson regression were pooled over all 5 cities. Particle number concentrations and PM10 averaged over 2 days (lag 0-1) were associated with increased total nontrauma mortality for patients of age 35 to 74 (5.6% [95% confidence interval, 2.8%-8.5%] per 10,000/cm and 5.1% [1.6%-9.3%] per 10 microg/m, respectively). For longer averaging times (5 and 15 days), carbon monoxide and nitrogen dioxide were also associated with mortality. There were no clear associations with ozone or sulfur dioxide. Exposure to traffic-related air pollution was associated with daily mortality in MI survivors. Point estimates suggest a stronger effect of air pollution in MI survivors than among the general population.

Heart Rate Variability, Ambient Particulate Matter Air Pollution, and Glucose Homeostasis: The Environmental Epidemiology of Arrhythmogenesis in the Women's Health Initiative

Heart Rate Variability, Ambient Particulate Matter Air Pollution, and Glucose Homeostasis: The Environmental Epidemiology of Arrhythmogenesis in the Women's Health Initiative

Effect of Atorvastatin on PM10-induced Cytokine Production by Human Alveolar Macrophages and Bronchial Epithelial Cells

Exposure to ambient air pollution particles (PM(10)) has been associated with increased cardiovascular morbidity and mortality. Inhaled pollutants induce a pulmonary and systemic inflammatory response that is thought to exacerbate cardiovascular disease. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to have anti-inflammatory effects that could contribute to their beneficial effect in cardiovascular disease. The aim of this study is to determine the effects of statins on PM(10)-induced cytokine production in human bronchial epithelial cells (HBECs) and alveolar macrophages (AMs). Primary HBECs and AMs are obtained from resected human lung. Cells are pretreated with different concentrations of atorvastatin for 24 hours and then exposed to 100 microg/mL urban air pollution particles (EHC-93). Cytokine levels (interleukin-1beta, interleukin-8, granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha) are measured at messenger RNA and protein levels using real-time polymerase chain reaction and bead-based multiplex immunoassay, respectively. PM(10) exposure increases production of these cytokines by both cell types. Atorvastatin attenuates PM(10)-induced messenger RNA expression and cytokine production by AMs but not by HBECs. It is concluded that statins can modulate the PM(10)-induced inflammatory response in the lung by reducing mediator production by AMs.

Spatial attenuation of ambient particulate matter air pollution within an urbanised native forest patch

Of interest to researchers and urban planners is the effect of urban forests on concentrations of ambient air pollution. Although estimates of the attenuation effect of urban vegetation on levels of air pollution have been put forward, there have been few monitored data on small-scale changes within forests, especially in urban forest patches. This study explores the spatial attenuation of particulate matter air pollution less than 10 μ in diameter (PM 10) within the confines of an evergreen broadleaved urban forest patch in Christchurch, New Zealand, a city with high levels of PM 10 winter air pollution. The monitoring network consisted of eight monitoring sites at various distances from the edge of the canopy and was operated on 13 winter nights when conditions were conducive for high pollution events. A negative gradient of particulate concentration was found, moving from higher mean PM10 concentrations outside the forest (mean=31.5 μg m −3) to lower concentrations deep within the forest (mean=22.4 μg m −3). A mixed-effects model applied to monitor meteorological, spatial and pollution data indicated temperature and an interaction between wind speed and temperature were also significant ( P⩽0.05) predictors of particulate concentration. These results provide evidence of the potential role that urban forest patches may play in mitigating particulate matter air pollution and should be considered in plans for improving urban air quality.

A panel study of air pollution in subjects with heart failure: negative results in treated patients

Objectives:To investigate preclinical adverse effects of ambient particulate air pollution and nitrogen oxides in patients with heart failure.Methods:A cohort of 132 non-smoking patients living in Aberdeen, Scotland, with stable chronic...

Ambient Particulate Air Pollution and Ectopy—The Environmental Epidemiology of Arrhythmogenesis in Women's Health Initiative Study, 1999–2004

The relationships between ambient PM2.5 and PM10 and arrhythmia and the effect modification by cigarette smoking were investigated. Data from U.S. Environmental Protection Agency (EPA) air quality monitors and an established national-scale, log-normal kriging method were used to spatially estimate daily mean concentrations of PM at addresses of 57,422 individuals from 59 examination sites in 24 U.S. states in 1999–2004. The acute and subacute exposures were estimated as mean, geocoded address-specific PM concentrations on the day of, 0–2 d before, and averaged over 30 d before the electrocardiogram (ECG) (Lag0; Lag1; Lag2; Lag1–30). At the time of standard 12-lead resting ECG, the mean age (SD) of participants was 67.5 (6.9) yr (84% non-Hispanic White; 6% current smoker; 15% with coronary heart disease; 5% with ectopy). After the identification of significant effect modifiers, two-stage random-effects models were used to calculate center-pooled odds ratios and 95% confidence intervals (OR, 95% CI) of arrhythmia per 10 μg/m3 increase in PM concentrations. Among current smokers, Lag0 and Lag1 PM concentrations were significantly associated ventricular ectopy (VE)—the OR (95% CI) for VE among current smokers was 2 (1.32–3.3) and 1.32 (1.07–1.65) at Lag1 PM2.5 and PM10, respectively. The interactions between current smoking and acute exposures (Lag0; Lag1; Lag2) were significant in relationship to VE. Acute exposures were not significantly associated with supraventricular ectopy (SVE), or with VE among nonsmokers. Subacute (Lag1–30) exposures were not significantly associated with arrhythmia. Acute PM2.5 and PM10 exposure is directly associated with the odds of VE among smokers, suggesting that they are more vulnerable to the arrhythmogenic effects of PM.

Asia: Changing Times and Changing Problems

Asia: Changing Times and Changing Problems

Associations between PM 2.5 and Heart Rate Variability Are Modified by Particle Composition and Beta-Blocker Use in Patients with Coronary Heart Disease

BackgroundIt has been hypothesized that ambient particulate air pollution is able to modify the autonomic nervous control of the heart, measured as heart rate variability (HRV). Previously we reported heterogeneous associations between particulate matter with aerodynamic diameter < 2.5 μm (PM2.5) and HRV across three study centers.ObjectivesWe evaluated whether exposure misclassification, effect modification by medication, or differences in particle composition could explain the inconsistencies.MethodsSubjects with coronary heart disease visited clinics biweekly in Amsterdam, the Netherlands; Erfurt, Germany; and Helsinki, Finland for 6–8 months. The standard deviation (SD) of NN intervals on an electrocardiogram (ECG; SDNN) and high frequency (HF) power of HRV was measured with ambulatory ECG during paced breathing. Outdoor levels of PM2.5 were measured at a central site. In Amsterdam and Helsinki, indoor and personal PM2.5 were measured during the 24 hr preceding the clinic visit. PM2.5 was apportioned between sources using principal component analyses. We analyzed associations of indoor/personal PM2.5, elements of PM2.5, and source-specific PM2.5 with HRV using linear regression.ResultsIndoor and personal PM2.5 were not associated with HRV. Increased outdoor PM2.5 was associated with decreased SDNN and HF at lags of 2 and 3 days only among persons not using beta-blocker medication. Traffic-related PM2.5 was associated with decreased SDNN, and long-range transported PM2.5 with decreased SDNN and HF, most strongly among persons not using beta blockers. Indicators for PM2.5 from traffic and long-range transport were also associated with decreased HRV.ConclusionsOur results suggest that differences in the composition of particles, beta-blocker use, and obesity of study subjects may explain some inconsistencies among previous studies on HRV.

The effect of ambient air pollution on respiratory health of school children: a panel study

BackgroundAdverse respiratory effects of particulate air pollution have been identified by epidemiological studies. We aimed to examine the health effects of ambient particulate air pollution from wood burning on school-age students in Christchurch, New Zealand, and to explore the utility of urine and exhaled breath condensate biomarkers of exposure in this population.MethodsA panel study of 93 male students (26 with asthma) living in the boarding house of a metropolitan school was undertaken in the winter of 2004. Indoor and outdoor pollution data was continuously monitored. Longitudinal assessment of lung function (FEV1 and peak flow) and symptoms were undertaken, with event studies of high pollution on biomarkers of exposure (urinary 1-hydroxypyrene) and effect (exhaled breath condensate (EBC) pH and hydrogen peroxide concentration).ResultsPeak levels of air pollution were associated with small but statistically significant effects on lung function in the asthmatic students, but not healthy students. No significant effect of pollution could be seen either on airway inflammation and oxidative stress either in healthy students or students with asthma. Minor increases in respiratory symptoms were associated with high pollution exposure. Urinary 1-hydroxypyrene levels were raised in association with pollution events by comparison with low pollution control days.ConclusionThere is no significant effect of ambient wood-smoke particulate air pollution on lung function of healthy school-aged students, but a small effect on respiratory symptoms. Asthmatic students show small effects of peak pollution levels on lung function. Urinary 1-hydroxypyrene shows potential as a biomarker of exposure to wood smoke in this population; however measurement of EBC pH and hydrogen peroxide appears not to be useful for assessment of population health effects of air pollution.Some of the data presented in this paper has previously been published in Kingham and co-workers Atmospheric Environment, 2006 Jan; 40: 338–347 (details of pollution exposure), and Cavanagh and co-workers Sci Total Environ. 2007 Mar 1;374(1):51-9 (urine hydroxypyrene data).

Traffic-related Particles Are Associated with Elevated Homocysteine

Recent epidemiologic studies have shown that homocysteine, a sulfur-containing amino acid formed during the metabolism of methionine, is a risk factor for atherosclerosis, myocardial infarction, stroke, and thrombosis. Particulate air pollution has been related to cardiovascular death and hospital admission, but the underlying mechanisms are not fully elucidated. We examined the associations between ambient particulate air pollution and plasma concentrations of homocysteine among 960 community-residing older men (mean age, 73.6 +/- 6.9 yr). Total homocysteine in plasma, measured using high-performance liquid chromatography with fluorescence detection, was regressed on each ambient particulate pollutant (black carbon, organic carbon, sulfate or PM(2.5)), and effect modification by plasma and dietary B vitamins (folate, B6, and B12) was examined. The median concentration of total homocysteine was 10.6 micromol/L. Statistically significant positive associations of total homocysteine were observed with traffic-related particles (black carbon and organic carbon). No association was observed with sulfate, an indicator of coal combustion particles, or PM(2.5) (particulate matter < or = 2.5 microm in aerodynamic diameter). The effects of black carbon and organic carbon were more pronounced in persons with low concentrations of plasma folate and vitamin B12. Exposures to ambient particles, particularly from traffic, are associated with elevated plasma total homocysteine. Homocysteine may be a component or biological marker of the oxidation pathways underlying the effect of ambient particles on the cardiovascular system.

Mechanism of asthmatic exacerbation by ambient air pollution particles

In the previous two to three decades, the prevalence of asthma has risen in numerous countries of the world. Correlating with this elevated prevalence of asthma, societies have observed increased air pollution from specific sources. Studies have implicated certain pollutants in asthmatic exacerbation. Particulate matter (PM) is the pollutant most frequently identified with worsening of this airway disease. PM is a temporally and spatially shifting suspension of solids and liquids originating from both natural and anthropogenic sources. Exposures to elevated levels of PM have been associated with asthmatic exacerbations by employing a diverse array of end points, including respiratory symptoms, use of medication, medical visits, emergency room visits, hospital admissions and pulmonary function decrements. Pertinent to worsening of asthma by ambient air PM, there are other particle-associated exposures that similarly precipitate asthmatic exacerbations. These include traffic-associated pollutants, diesel exhaust, emissions from gas and wood stoves, burning of biomass and environmental tobacco smoke. It is widely accepted that the biological effects exerted by all particle exposures result from oxidative stress. This stimulates cell signaling, transcription factor activation and mediator release in the respiratory tract, culminating in inflammation. Other postulated mechanisms for asthmatic exacerbation following PM exposure include an impact on the incidence of infections and adjuvant effects.

Ambient Particulate Air Pollution and Ectopy—The Environmental Epidemiology of Arrhythmogenesis in Women's Health Initiative Study, 1999–2004

Ambient Particulate Air Pollution and Ectopy—The Environmental Epidemiology of Arrhythmogenesis in Women's Health Initiative Study, 1999–2004

Ambient Air Pollution Particles and the Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air pollution particles. Current and ex-smokers account for 80 to 85% of all those with COPD. The human breathing in an urban site with a significant level of particulate matter (PM) may be exposed to 720 μ g daily. A single cigarette introduces 15,000 to 40,000 μ g particle into the respiratory tract of the smoker. It is subsequently confounding why such a relatively small mass of airborne PM should have any biological effect in the patient with COPD, as these individuals are repeatedly exposed to particles (with a similar size and composition) at perhaps a thousandfold the mass of ambient PM. Regarding this increased sensitivity of COPD patients to air pollution particles, there are several possible explanations for this seeming contradiction, including correlations of PM levels with other components of air pollution, an accumulation of multiple independent risk factors in a patient, changes in individual activity patterns, disparities in dosimetry between healthy subjects and COPD patients, and some unique characteristic of an ambient air pollution PM. Regardless of the underlying mechanism for the increased sensitivity of COPD patients, exposures of these individuals to elevated levels of PM should be discouraged. To provide a greater awareness of PM levels, the U.S. Environmental Protection Agency now includes levels of air pollution particles in an air quality index.

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques

Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously showed that PM(10) exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of atherosclerosis.

Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis pathways

The epidemiological association between cancer and exposure to ambient air pollution particles (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10))) has been related to the ability of PM(10) and its constituent nanoparticles (NPs) to cause reactive oxidative species (ROS)-driven DNA damage. However, there are no data on the molecular response to these genotoxic effects. In order to assess whether PM(10), NP and ROS-driven DNA damage induce carcinogenesis pathways, A549 cells were treated with tert-butyl-hyperperoxide (Tbh), urban dust (UD), carbon black (CB), nanoparticulate CB (NPCB), benzo(a)pyrene (BaP) and NPCB coated with BaP for <or=24 h. Single- and double-strand breakage of DNA was determined by comet assay; cell cycle status was analysed using flow cytometry. Nuclear extracts or acid-extracted histones were used for Western blot analysis of p-ser15-p53 (p53 phosphorylated at ser15), p53 binding protein (53BP) 1, phospho-histone H2A.X (p-H2A.X) and phospho-BRCA1 (p-BRCA1). UD caused both single- and double-strand DNA breaks, while other tested NPs caused only single-strand DNA breaks. NPs significantly altered cell cycle kinetics. Tbh enhanced p-H2A.X after 1 and 6 h (2.1- and 2.2-fold, respectively). NP increased 53BP1 expression at 1 h (2.4-8.7-fold) and p-BRCA1 at 1-6 h. N-acetylcysteine blocked NP-driven p-ser15-p53 response. In conclusion, nanoparticles and reactive oxidative species induce DNA damage, activating p53 and proteins related to DNA repair, mimicking irradiation-related carcinogenesis pathways.