This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.particleandfibretoxicology.com The latest articles from Particle and Fibre Toxicology (ISSN 1743-8977) published by BioMed Central Background: Particulate air pollution is associated with increased risk of cardiovascular events although the involved mechanisms are poorly understood. ObjectiveTo investigate the effects of controlled exposure to ambient air fine and ultrafine particles on microvascular function and biomarkers related to inflammation, hemostasis and lipid and protein oxidation. Design and methods. Twenty-nine subjects participated in a randomized, two-factor crossover study with or without biking exercise for 180 minutes and with 24 hour exposure to particle rich (number concentrations, NC: 6169-15362 per cm3) or particle filtered (NC: 91-542 per cm3) air collected above a busy street. Microvascular function was assessed non-invasively by measuring digital peripheral artery tone following arm ischemia. Biomarkers included hemoglobin, red blood cells, platelet count, coagulation factors, C-reactive protein, fibrinogen, interleukin-6, tumor necrosis factor alpha, lag time to copper-induced oxidation of plasma lipids and protein oxidation measured as 2-aminoadipic semialdehyde in plasma. Results: No statistically significant effects of exposure were observed on microvascular function or the biomarkers. Conclusion: This study indicates that exposure to air pollution particles at outdoor concentrations for up to 24 hours is not associated with detectable systemic inflammation, lipid or protein oxidation, altered hemostasis or microvascular function in young healthy participants. http://www.particleandfibretoxicology.com/content/5/1/13 Elvira V Brauner, Peter Moller, Lars Barregard, Lars O Dragsted, Marianne Glasius, Peter Wahlin, Peter Vinzents, Ole Raaschou-Nielsen and Steffen Loft Particle and Fibre Toxicology 2008, 5:13 2008-10-06 doi:10.1186/1743-8977-5-13 Particle and Fibre Toxicology 1743-8977 5 13 2008-10-06 Background: Welding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 μg of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.5 μg soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure. Results: BAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the fumes. At 48 weeks, carcinogenic metal-containing GMA-SS fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this fume in lung cells compared to the other welding fumes was found. Conclusion: The increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain. http://www.particleandfibretoxicology.com/content/5/1/12 Patti C Zeidler-Erdely, Michael L Kashon, Lori A Battelli, Shih-Houng Young, Aaron Erdely, Jenny R Roberts, Steven H Reynolds and James M Antonini Particle and Fibre Toxicology 2008, 5:12 2008-09-08 doi:10.1186/1743-8977-5-12 Particle and Fibre Toxicology 1743-8977 5 12 2008-09-08 This is a reply to a letter of the Editor by Valberg et al. http://www.particleandfibretoxicology.com/content/5/1/11 Björn Crüts, Anique Driessen, Ludo van Etten, Håkan Törnqvist, Anders Blomberg, Thomas Sandström, Nicholas L Mills and Paul JA Borm Particle and Fibre Toxicology 2008, 5:11 2008-08-02 doi:10.1186/1743-8977-5-11 Particle and Fibre Toxicology 1743-8977 5 11 2008-08-02 A recent publication in this journal reported interesting changes in electroencephalographic (EEG) waves that occurred in 10 young, male volunteers following inhalation for one hour of elevated levels of diesel-engine exhaust fumes 1. The authors then proposed a chain of causal events that they hypothesized underlay their observed EEG changes. Their reasoning linked the observed results to nanoparticles in diesel-engine exhaust (DEE), and went on to suggest that associations between changes in ambient particulate matter (PM) levels and changes in health statistics might be due to the effects of diesel-engine exhaust (DEE) nanoparticles on EEG. We suggest that the extrapolations of the Crüts et al. EEG findings to casual mechanisms about how ambient levels of DEE particulate might affect electrical signals in the brain, and subsequently to how DEE particulate might alter disease risk, are premature. http://www.particleandfibretoxicology.com/content/5/1/10 Peter A Valberg, Christopher M Long and Thomas W Hesterberg Particle and Fibre Toxicology 2008, 5:10 2008-07-24 doi:10.1186/1743-8977-5-10 Particle and Fibre Toxicology 1743-8977 5 10 2008-07-24 Background: The potential of diesel soot aerosol particles to break up into smaller units under mechanical stress was investigated by a direct impaction technique which measures the degree of fragmentation of individual agglomerates vs. impact energy. Diesel aerosol was generated by an idling diesel engine used for passenger vehicles. Both the aerosol emitted directly and aerosol that had undergone additional growth by Brownian coagulation ("aging") was investigated. Optionally a thermo-desoption technique at 280°C was used to remove all high-volatility and the majority of low-volatility HC adsorbates from the aerosol before aging. Results: It was found that the primary soot agglomerates emitted directly from the engine could not be fragmented at all. Soot agglomerates permitted to grow additionally by Brownian coagulation of the primary emitted particles could be fragmented to a maximum of 75% and 60% respectively, depending on whether adsorbates were removed from their surface prior to aging or not. At most, these aged agglomerates could be broken down to roughly the size of the agglomerates from the primary emission. The energy required for a 50% fragmentation probability of all bonds within an agglomerate was reduced by roughly a factor of 2 when aging "dry" agglomerates. Average bond energies derived from the data were 0.52*10-16 and 1.2*10-16 J, respectively. This is about 2 orders of magnitude higher than estimates for pure van-der-Waals agglomerates, but agrees quite well with other observations. Conclusion: Although direct conclusions regarding the behavior of inhaled diesel aerosol in contact with body fluids cannot be drawn from such measurements, the results imply that highly agglomerated soot aerosol particles are unlikely to break up into units smaller than roughly the size distribution emitted as tail pipe soot. http://www.particleandfibretoxicology.com/content/5/1/9 Sonja Rothenbacher, Armin Messerer and Gerhard Kasper Particle and Fibre Toxicology 2008, 5:9 2008-06-04 doi:10.1186/1743-8977-5-9 Particle and Fibre Toxicology 1743-8977 5 9 2008-06-04 Background: Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is a major contributor to particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, together with an enhanced epithelial expression of cytokines such as IL-8, Gro-α, IL-13 and activation of redox sensitive transcription factors (NFκB, AP-1), and MAP kinases (p38, JNK). The aim of the present investigation was to elucidate the involvement of the epidermal growth factor receptor (EGFR) signalling pathway in the epithelial response to DE in-vivo. Results: Immunohistochemical staining was used to quantify the expression of the EGFR, phosphorylated Tyrosine residues, MEK and ERK in the bronchial epithelium of archived biopsies from 15 healthy subjects following exposure to DE (PM10, 300 μg/m3) and air. DE induced a significant increases in the expression of EGFR (p = 0.004) and phosphorylated C-terminal Tyr 1173 (p = 0.02). Other investigated EGFR tyrosine residues, Src related tyrosine (Tyr 416), MEK and ERK pathway were not changed significantly by DE. Conclusion: Exposure to DE (PM10, 300 μg/m3) caused enhanced EGFR expression and phosphorylation of the tyrosine residue (Tyr 1173) which is in accordance with the previously demonstrated activation of the JNK, AP-1, p38 MAPK and NFkB pathways and associated downstream signalling and cytokine production. No effects were seen on the MEK and ERK pathway suggesting that at the investigated time point (6 hours post exposure) there was no proliferative/differentiation signalling in the bronchial epithelium. The present findings suggest a key role for EGFR in the bronchial response to diesel exhaust. http://www.particleandfibretoxicology.com/content/5/1/8 Jamshid Pourazar, Anders Blomberg, Frank J Kelly, Donna E Davies, Susan J Wilson, Stephen T Holgate and Thomas Sandström Particle and Fibre Toxicology 2008, 5:8 2008-05-06 doi:10.1186/1743-8977-5-8 Particle and Fibre Toxicology 1743-8977 5 8 2008-05-06 Background: Alveolar macrophages (AM) avidly bind and ingest unopsonized inhaled particles and bacteria through class A scavenger receptors (SRAs) MARCO and SR-AI/II. Studies to characterize the function of these SRAs have used AMs from MARCO or SR-AI/II null mice, but this approach is limited by the relatively low yield of AMs. Moreover, studies using both MARCO and SR-AI/II-deficient (MS-/-) mice have not been reported yet. Hence, we sought to develop continuous cell lines from primary alveolar macrophages from MS-/- mice. Results: We used in vitro infection of the primary AMs with the J2 retrovirus carrying the v-raf and v-myc oncogenes. Following initial isolation in media supplemented with murine macrophage colony-stimulating factor (M-CSF), we subcloned three AM cell lines, designated ZK-1, ZK-2 and ZK-6. These cell lines grow well in RPMI-1640-10% FBS in the absence of M-CSF. These adherent but trypsin-sensitive cell lines have a doubling time of approximately 14 hours, exhibit typical macrophage morphology, and express macrophage-associated cell surface Mac-1 (CD11b) and F4/80 antigens. The cell lines show robust Fc-receptor dependent phagocytosis of opsonized red blood cells. Similar to freshly isolated AMs from MS-/- mice, the cell lines exhibit decreased phagocytosis of unopsonized titanium dioxide (TiO2), fluorescent latex beads and bacteria (Staphylococcus aureus) compared with the primary AMs from wild type (WT) C57BL/6 mice. Conclusion: Our results indicated that three contiguous murine alveolar macrophage cell lines with MS-/- (ZK1, ZK2 and ZK6) were established successfully. These cell lines demonstrated macrophage morphology and functional activity. Interestingly, similar to freshly isolated AMs from MS-/- mice, the cell lines have a reduced, but not absent, ability to bind and ingest particles, with an altered pattern of blockade by scavenger receptor inhibitors. These cell lines will facilitate in vitro studies to further define MARCO and SR-AI/II function, and may also be useful to identify other novel scavenger-type macrophage receptors and for additional studies of particle toxicology. http://www.particleandfibretoxicology.com/content/5/1/7 Hongwei Zhou, Amy Imrich and Lester Kobzik Particle and Fibre Toxicology 2008, 5:7 2008-05-02 doi:10.1186/1743-8977-5-7 Particle and Fibre Toxicology 1743-8977 5 7 2008-05-02 Background: Exposure to air pollution particles has been acknowledged to be associated with excess generation of oxidative damage to DNA in experimental model systems and humans. The use of standard reference material (SRM), such as SRM1650 and SRM2975, is advantageous because experiments can be reproduced independently, but exposure to such samples may not mimic the effects observed after exposure to authentic air pollution particles. This study was designed to compare the DNA oxidizing effects of authentic street particles with SRM1650 and SRM2975. The authentic street particles were collected at a traffic intensive road in Copenhagen, Denmark. Results: All of the particles generated strand breaks and oxidized purines in A549 lung epithelial cells in a dose-dependent manner and there were no overt differences in their potency. The exposures also yielded dose-dependent increase of cytotoxicity (as lactate dehydrogenase release) and reduced colony forming ability with slightly stronger cytotoxicity of SRM1650 than of the other particles. In contrast, only the authentic street particles were able to generate 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in calf thymus DNA, which might be due to the much higher level of transition metals. Conclusion: Authentic street particles and SRMs differ in their ability to oxidize DNA in a cell-free environment, whereas cell culture experiments indicate that the particle preparations elicit a similar alteration of the level of DNA damage and small differences in cytotoxicity. Although it cannot be ruled out that SRMs and authentic street particles might elicit different effects in animal experimental models, this study indicates that on the cellular level, SRM1650 and SRM2975 are suitable surrogate samples for the study of authentic street particles. http://www.particleandfibretoxicology.com/content/5/1/6 Pernille Høgh Danielsen, Steffen Loft and Peter Møller Particle and Fibre Toxicology 2008, 5:6 2008-04-08 doi:10.1186/1743-8977-5-6 Particle and Fibre Toxicology 1743-8977 5 6 2008-04-08 Particle and Fibre Toxicology (PFT) is active as the only open access journal in its field. The new Editor-in-Chief describes why PFT is the forum for interaction in the rapidly evolving field ofparticle toxicology. Scientists in nanomedicine, material science, and others engineering nanoparticles are encouraged to share their know-how on toxicology with those that typically considered inhaled particles. http://www.particleandfibretoxicology.com/content/5/1/5 Paul JA Borm Particle and Fibre Toxicology 2008, 5:5 2008-04-07 doi:10.1186/1743-8977-5-5 Particle and Fibre Toxicology 1743-8977 5 5 2008-04-07 Background: Ambient particulate matter and nanoparticles have been shown to translocate to the brain, and potentially influence the central nervous system. No data are available whether this may lead to functional changes in the brain. Methods: We exposed 10 human volunteers to dilute diesel exhaust (DE, 300 μg/m3) as a model for ambient PM exposure and filtered air for one hour using a double blind randomized crossover design. Brain activity was monitored during and for one hour following each exposure using quantitative electroencephalography (QEEG) at 8 different sites on the scalp. The frequency spectrum of the EEG signals was used to calculate the median power frequency (MPF) and specific frequency bands of the QEEG. Results: Our data demonstrate a significant increase in MPF in response to DE in the frontal cortex within 30 min into exposure. The increase in MPF is primarily caused by an increase in fast wave activity (β2) and continues to rise during the 1 hour post-exposure interval. Conclusion: This study is the first to show a functional effect of DE exposure in the human brain, indicating a general cortical stress response. Further studies are required to determine whether this effect is mediated by the nanoparticles in DE and to define the precise pathways involved. http://www.particleandfibretoxicology.com/content/5/1/4 Björn Crüts, Ludo van Etten, Håkan Törnqvist, Anders Blomberg, Thomas Sandström, Nicholas L Mills and Paul JA Borm Particle and Fibre Toxicology 2008, 5:4 2008-03-11 doi:10.1186/1743-8977-5-4 Particle and Fibre Toxicology 1743-8977 5 4 2008-03-11