Particulates are small particles of solid or liquid suspended in liquid or air. In vitro studies show that particles generate reactive oxygen species, deplete endogenous antioxidants, alter mitochondrial function and produce oxidative damage to lipids and DNA. Surface area, reactivity and chemical composition play important roles in the oxidative potential of particulates. Studies in animal models indicate that particles from combustion processes (generated by combustion of wood or diesel oil), silicate, titanium dioxide and nanoparticles (C60 fullerenes and carbon nanotubes) produce elevated levels of lipid peroxidation products and oxidatively damaged DNA. Biomonitoring studies in humans have shown associations between exposure to air pollution and wood smoke particulates and oxidative damage to DNA, deoxynucleotides and lipids measured in leukocytes, plasma, urine and/or exhaled breath. The results indicate that oxidative stress and elevated levels of oxidatively altered biomolecules are important intermediate endpoints that may be useful markers in hazard characterization of particulates.

Manufactured nanomaterials are projected to be used on a large scale in paints and lacquers. We selected seven commercially interesting materials: Three titanium dioxide-based (two coated rutile; one uncoated anatase), one carbon black (Flamrüss 101), one kaolinite clay, and two silica products, whereas carbon black, Printex 90, was used as reference material. DNA damaging activity and inflammogenicity (pulmonary cell composition and mRNAs) were determined 24 h after intratracheal instillation of a single dose of 54 μg in mice. Greatest inflammation was induced by Printex 90 and uncoated titanium dioxide. The inflammatory potency correlated with instilled surface area (R(2) = 0.94) but not with material volume (R(2) = 0.17). The coated titanium dioxides induced DNA damage in lung lining fluid cells. The uncoated titanium dioxide was not DNA damaging by the comet assay 24 h after exposure despite being highly inflammogenic. This suggests that inflammation is not a prerequisite to DNA damage in titanium dioxide-based products.

Accumulating evidences indicate that pulmonary exposure to carbon nanotubes (CNTs) is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of 2 types of multiwalled CNTs (MWCNTs) in apolipoprotein E(-/-) mice, wild-type mice, and cultured cells. The ApoE(-/-) mice had accelerated plaque progression in aorta after 5 intracheal instillations of MWCNT (25.6 μg/mouse weekly for 5 weeks). The exposure was associated with pulmonary inflammation, lipid peroxidation, and increased expression of inflammatory, oxidative stress, DNA repair, and vascular activation response genes. The level of oxidatively damaged DNA in lung tissue was unaltered, probably due to increased DNA repair capacities. Despite upregulation of inflammatory genes in the liver, effects on systemic cytokines and lipid peroxidation were minimal. The exposure to MWCNTs in cultured human endothelial cells increased the expression of cell adhesion molecules (ICAM1 and VCAM1). In cocultures, there was increased adhesion of monocytes to endothelial cells after exposure to MWCNT. The exposure to both types of MWCNT was also associated with increased lipid accumulation in monocytic-derived foam cells, which was dependent on concomitant oxidative stress because the antioxidant N-acetylcysteine inhibited the lipid accumulation. Collectively, our results indicate that exposure to MWCNT is associated with accelerated progression of atherosclerosis, which could be related to both increased adherence of monocytes onto the endothelium and oxidative stress-mediated transformation of monocytes to foam cells.

Nanoparticles are increasingly used in paints and lacquers. Little is known of the toxicity of nanoparticles incorporated in complex matrices and released during different phases of the life cycle. DNA damaging activity and inflammogenicity of sanding dust sampled during standardised sanding of boards painted with paints with and without nanoparticles were determined 24 h after intratracheal instillation of a single dose of 54 μg in mice. Dusts from nanoparticle-containing paints and lacquers did not generate pulmonary inflammation or oxidative stress. Sanding dust from both the nanoparticle-containing and the conventional lacquer and the outdoor acrylic-based reference paint increased the level of DNA strand breaks in bronchoalveolar fluid cells. In conclusion, addition of nanoparticles to paint or lacquers did not increase the potential of sanding dust for causing inflammation, oxidative stress or DNA damage, suggesting that the paint/lacquer matrix is more important as determinant of DNA damage than the nanomaterial.

BackgroundThere is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.MethodsWe investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE-/-) mice exposed to TiO2. ApoE-/- mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO2 (fTiO2, 288 nm), photocatalytic 92/8 anatase/rutile TiO2 (pTiO2, 12 nm), or rutile nano TiO2 (nTiO2, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO2 (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO2-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs).ResultsThe exposure to nTiO2 was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE-/- mice exposed to fine and photocatalytic TiO2 had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO2.ConclusionRepeated exposure to nanosized TiO2 particles was associated with modest plaque progression in ApoE-/- mice. There were no associations between the pulmonary TiO2 exposure and inflammation or vasodilatory dysfunction.