Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells. (17/958)

We have previously shown that exposure to diesel exhaust particles (DEPs) stimulates human airway epithelial cells to secrete the inflammatory cytokines interleukin-8, interleukin-1beta, and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in allergic diseases. In the present paper, we studied the mechanisms underlying the increase in GM-CSF release elicited by DEPs using the human bronchial epithelial cell line 16HBE14o-. RT-PCR analysis has shown an increase in GM-CSF mRNA levels after DEP treatments. Comparison of the effects of DEPs, extracted DEPs, or extracts of DEPs has shown that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and not to the metals present on the DEP surface because the metal chelator desferrioxamine had no inhibitory effect. Furthermore, radical scavengers inhibited the DEP-induced GM-CSF release, showing involvement of reactive oxygen species in this response. Moreover genistein, a tyrosine kinase inhibitor, abrogated the effects of DEPs on GM-CSF release, whereas protein kinase (PK) C, PKA, cyclooxygenase, or lipoxygenase inhibitors had no effect. PD-98059, an inhibitor of mitogen-activated protein kinase, diminished the effects of DEPs, whereas SB-203580, an inhibitor of p38 mitogen-activated protein kinase, had a lower effect, and DEPs did actually increase the active, phosphorylated form of the extracellular signal-regulated kinase as shown by Western blotting. In addition, cytochalasin D, which inhibits the phagocytosis of DEPs, reduced the increase in GM-CSF release after DEP treatment. Together, these data suggest that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and that the effect of native DEPs requires endocytosis of the particles. Reactive oxygen species and tyrosine kinase(s) may be involved in the DEP-triggered signaling of the GM-CSF response.  (+info)

Bioreactivity of carbon black and diesel exhaust particles to primary Clara and type II epithelial cell cultures. (18/958)

OBJECTIVES: To begin to elucidate the mechanisms of particle toxicity to the lung, the bioreactivity of four carbon black (CB) and diesel exhaust particles ((DEPs), a surrogate for particulate matter of aerodynamic diameter < 10 microns (PM10), were examined with primary cultures of Clara and type II epithelial cells. METHODS: The particles were extensively characterised by surface chemistry, size, and aggregation properties. Toxicity of the particles was assessed by determining cell attachment to an extracellular matrix substratum. RESULTS: The spherulite size range for the particles ranged from 50, 40, 20, 20, and 30 nm for CB1-4 and DEPs. All particle samples had different surface chemical compositions. CB1 was the least toxic to Clara (170 micrograms) and type II cells (150 micrograms) and CB4 was the most toxic (55 micrograms and 23 micrograms respectively). DEPs stored for 2 weeks were equally toxic to both epithelial cell types (27-28 micrograms). DEPs became progressively less toxic to type II cells with time of storage. Both primary epithelial cell types internalised the particles in culture. CONCLUSIONS: Bioreactivity was found to be related to CB particle spherulite size and hence surface area: the smaller the particle and larger the surface area, the more toxic the particles. Also, CB particles with the most complicated surface chemistry were the most bioreactive. Freshly prepared DEPs were equally toxic to type II and Clara cells and they became progressively less toxic to the type II cells with time. With all CB and DEPs, the primary epithelial cells internalised the particles, although this was noted most in cells of low functional competence.  (+info)

Occupational lung cancer risk for men in Germany: results from a pooled case-control study. (19/958)

Occupational exposures such as crystalline silica, diesel engine exhaust, polycyclic aromatic hydrocarbons, and man-made mineral fibers are strongly suspected to increase lung cancer risk. Two case-control studies in Germany conducted between 1988 and 1996 were pooled for a joint analysis. A total of 3,498 male cases and 3,541 male population controls, frequency matched for age and region, were included in the study. The lifelong history of all jobs and industries was coded and occupational exposures were evaluated by expert rating. Odds ratios, crude and adjusted for smoking and asbestos exposure, were calculated by conditional logistic regression. Job-related evaluation showed a statistically significant increased odds ratio adjusted for smoking among farmers; forestry workers, fishermen, and livestock workers; miners and quarrymen; chemical processors; cabinet makers and related wood workers; metal producers and processors; bricklayers and carpenters; road construction workers, pipelayers and well diggers; plasterers, insulators, and upholsterers; painters and lacquerers; stationary engine and heavy equipment operators; transport workers and freight handlers; and service workers. With regard to specific occupational exposures, elevated odds ratios (OR) (95% confidence intervals (CI)) for lung cancer risk adjusted for smoking and asbestos exposure were observed for man-made mineral fibers (OR = 1.48, 95% CI 1.17, 1.88); crystalline silica (OR = 1.41, 95% CI 1.22, 1.62); diesel engine exhaust (OR = 1.43, 95% CI 1.23, 1.67); and polycyclic aromatic hydrocarbons (OR = 1.53, 95% CI 1.14, 2.04). The risk of asbestos exposure, adjusted for smoking was also increased (OR = 1.41, 95% CI 1.24, 1.60).  (+info)

Personal exposure to JP-8 jet fuel vapors and exhaust at air force bases. (20/958)

JP-8 jet fuel (similar to commercial/international jet A-1 fuel) is the standard military fuel for all types of vehicles, including the U.S. Air Force aircraft inventory. As such, JP-8 presents the most common chemical exposure in the Air Force, particularly for flight and ground crew personnel during preflight operations and for maintenance personnel performing routine tasks. Personal exposure at an Air Force base occurs through occupational exposure for personnel involved with fuel and aircraft handling and/or through incidental exposure, primarily through inhalation of ambient fuel vapors. Because JP-8 is less volatile than its predecessor fuel (JP-4), contact with liquid fuel on skin and clothing may result in prolonged exposure. The slowly evaporating JP-8 fuel tends to linger on exposed personnel during their interaction with their previously unexposed colleagues. To begin to assess the relative exposures, we made ambient air measurements and used recently developed methods for collecting exhaled breath in special containers. We then analyzed for certain volatile marker compounds for JP-8, as well as for some aromatic hydrocarbons (especially benzene) that are related to long-term health risks. Ambient samples were collected by using compact, battery-operated, personal whole-air samplers that have recently been developed as commercial products; breath samples were collected using our single-breath canister method that uses 1-L canisters fitted with valves and small disposable breathing tubes. We collected breath samples from various groups of Air Force personnel and found a demonstrable JP-8 exposure for all subjects, ranging from slight elevations as compared to a control cohort to > 100 [mutilpe] the control values. This work suggests that further studies should be performed on specific issues to obtain pertinent exposure data. The data can be applied to assessments of health outcomes and to recommendations for changes in the use of personal protective equipment that optimize risk reduction without undue impact on a mission.  (+info)

Airborne concentrations of PM(2.5) and diesel exhaust particles on Harlem sidewalks: a community-based pilot study. (21/958)

Residents of the dense urban core neighborhoods of New York City (NYC) have expressed increasing concern about the potential human health impacts of diesel vehicle emissions. We measured concentrations of particulate matter [less than/equal to] 2.5 micro in aerodynamic diameter (PM(2.5)) and diesel exhaust particles (DEP) on sidewalks in Harlem, NYC, and tested whether spatial variations in concentrations were related to local diesel traffic density. Eight-hour (1000-1800 hr) air samples for PM(2.5 )and elemental carbon (EC) were collected for 5 days in July 1996 on sidewalks adjacent to four geographically distinct Harlem intersections. Samples were taken using portable monitors worn by study staff. Simultaneous traffic counts for diesel trucks, buses, cars, and pedestrians were carried out at each intersection on [Greater/equal to] 2 of the 5 sampling days. Eight-hour diesel vehicle counts ranged from 61 to 2,467 across the four sites. Mean concentrations of PM(2.5) exhibited only modest site-to-site variation (37-47 microg/m(3)), reflecting the importance of broader regional sources of PM(2.5). In contrast, EC concentrations varied 4-fold across sites (from 1.5 to 6 microg/m(3)), and were associated with bus and truck counts on adjacent streets and, at one site, with the presence of a bus depot. A high correlation (r = 0.95) was observed between EC concentrations measured analytically and a blackness measurement based on PM(2.5) filter reflectance, suggesting the utility of the latter as a surrogate measure of DEP in future community-based studies. These results show that local diesel sources in Harlem create spatial variations in sidewalk concentrations of DEP. The study also demonstrates the feasibility of a new paradigm for community-based research involving full and active partnership between academic scientists and community-based organizations.  (+info)

Corporate action to reduce air pollution--Atlanta, Georgia, 1998-1999. (22/958)

Ground-level ozone, a colorless gas, is a major constituent of smog. Since the early 1980s, controlled studies have demonstrated that exposure to elevated levels of ozone reduces inspiratory capacity in humans. In addition, ecologic analyses have indicated that daily emergency department visits for asthma exacerbations are elevated following days of high ozone pollution. The Partnership for a Smog-Free Georgia (PSG) is a state-sponsored program to reduce the number of days that ground-level ozone exceeds the national ambient air quality standard (NAAQS) in metropolitan Atlanta by providing federal and state subsidized commuting alternatives for local business employees. This report summarizes commuter data from three PSG partners to estimate reductions in emissions and monthly vehicle miles traveled that were associated with enrollment in PSG.  (+info)

Increase in mutation frequency in lung of Big Blue rat by exposure to diesel exhaust. (23/958)

Exposure to diesel exhaust (DE) is known to cause lung tumors in rats. To clarify the mutagenicity of DE, we estimated mutant frequency (MF) and determined the mutation spectra in rat lung after exposure to DE using lambda/lacI transgenic rats (Big Blue system). Male Big Blue rats (6 weeks old) were exposed for 4 weeks to 1 or 6 mg/m(3) DE, which contains suspended particulate matter. Control rats were maintained in filtered clean air. After exposure to 6 mg/m(3) DE, MF in lung was 4.8-fold higher than in control rats (P < 0.01), but no increase in MF was observed in rats exposed to 1 mg/m(3) DE. Sixty-nine mutants were identified after exposure to 6 mg/m(3) DE. The major mutations were A:T-->G:C (18 mutations) and G:C-->A:T (19 mutations) transitions. Remarkably, G-->T transversion of the lacI gene at site 221 was a hot-spot induced by exposure to DE, and there were complex mutations in which multiple mutations occurred in a single mutant, especially in the rats exposed to 6 mg/m(3) DE. DNA adducts formed by DE were analyzed using a (32)P-post-label TLC method and the amount of 8-hydroxydeoxyguanosine (8-OHdG) was measured using HPLC. Relative adduct level and amount of 8-OHdG were significantly increased in the rats exposed to 6 mg/m(3) DE compared with the controls (3.0- and 2.2-fold, respectively; P < 0.01). The level of cytochrome P450 1A1 mRNA was shown by northern blot analysis to be significantly increased in the lungs of rats exposed to 6 mg/m(3) DE (5.5-fold; P < 0.01). These results indicate that DE causes lesions in genomic DNA and acts as a mutagen in rat lung.  (+info)

Short-term exposure to air pollution in a road tunnel enhances the asthmatic response to allergen. (24/958)

The aim of this study was to assess whether air pollution in road tunnels would promote asthmatic reactions in persons with mild allergic asthma. Twenty volunteers with mild allergic asthma were exposed, inside a car, for 30 min in a Stockholm city road tunnel. As a control, the subjects were exposed to much lower pollution levels in a suburban area. Four hours after the exposure, the subjects inhaled a low dose of allergen. Asthmatic reaction during the early phase was measured as the increase in specific airway resistance 15 min after allergen inhalation and during the late phase as the decrease in lung function forced expiratory volume in one second 3-10 h after allergen inhalation. Asthma symptoms and drug use were monitored up to 18 h after allergen inhalation. The median nitrogen dioxide level during exposure was 313 microg x m-3 (range 203-462). The median levels of particles with 50% cut-off aerodynamic diameters of 10 (PM10) and 2.5 microm (PM2.5) were 170 (range 103-613) and 95 (range 61-218) micro x m-3, respectively. Subjective symptoms during tunnel exposure were not pronounced. However, subjects exposed to tunnel N02 levels of > or = 300 microg x m-3 had a significantly greater early reaction, following allergen exposure, as well as lower lung function and more asthma symptoms during the late phase, compared to control. Also, subjects with PM2.5 exposure > or = 100 microg x m-3 had a slightly increased early reaction compared to control. In conclusion, exposure to air pollution in road tunnels may significantly enhance asthmatic reactions to subsequently inhaled allergens.  (+info)