No abstract

Relatively low concentrations of reactive oxygen cause reversible alterations of endothelial cell signal transduction and gene transcription. The hypothesis that low levels of oxidant stress activate retention of trans-acting proteins in the nucleus was investigated by determining time and dose requirements for oxidant-stimulated nuclear protein binding to consensus DNA sequences for nuclear factor (NF)-kappa B or activator protein 1 (AP-1). Nuclear proteins were extracted from low passage porcine aortic endothelial cells 15 min to 24 h after addition of increasing concentrations of H2O2. Electrophoretic mobility shift assays demonstrated that protein binding to NF-kappa B and AP-1 sequences increases over 1-2 h after stress relative to time-matched controls and resolves by 24 h. The selective protein kinase C inhibitor, calphostin C, prevents approximately 30% of this increase. Inhibition of tyrosine kinase activity by herbimycin A (5 microM) completely inhibits the response to H2O2. Exposure of intact cells to H2O2 increases substrate phosphorylation in pp60src immunoprecipitates. The activity of pp60src in immunoprecipitates from control cells or of recombinant pp60src increases after in vitro addition of H2O2. H2O2-stimulated pp60src activity is reduced by pretreatment of the enzyme preparation with N-acetylcysteine. These data indicate that oxidants increase nuclear levels of trans-acting factors in endothelial cells and that these increases require oxidant-sensitive changes in both tyrosine and serine/threonine phosphorylations.

Nuclear factor icB (NF-icB) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation-features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-#cB-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-icB family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-icB-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced transcriptional activation of NF-#cB-dependent genes, an observation that was confirmed by Northern blot analyses for c-myc mRNA levels in HTE cells. Studies suggest that NF-ecB induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers.

Many organizations interested in renewable, domestic energy have switched from petroleum diesel to biodiesel blends for use in transportation and heavy-duty equipment. Although considerable evidence exists on the negative health effects of petroleum diesel exhaust exposures in occupational settings, there has been little research examining biodiesel exposures. Working collaboratively with a local municipality, concentrations of particulate matter (PM) and other air toxics were measured at a recycling facility in southwestern New Hampshire while heavy equipment operated first on petroleum diesel and then on a B20 blend (20% soy-based biodiesel/80% petroleum diesel). This pilot study used a combination of established industrial hygiene and environmental air monitoring methods to estimate occupational exposure profiles to PM and air toxics from combustion of petroleum diesel and biodiesel. Results indicate that B20 use dramatically reduces work area respirable particle, PM2.5 (PM ≤2.5 µm in aerodynamic diameter), and formaldehyde levels compared with petroleum diesel. Some volatile organic compound concentrations were higher for petroleum diesel and others were higher for the B20 blend. Overall, this study suggests that biodiesel blends reduce worker exposure to and health risk from petroleum diesel exhaust, but additional exposure research is recommended.

Many organizations are interested in biodiesel as a renewable, domestic energy source for use in transportation and heavy-duty equipment. Although numerous biodiesel emission studies exist, biodiesel exposure studies are nearly absent from the literature. This study compared the impact of petroleum diesel fuel and a B20 blend (20% soy-based biodiesel/80% petroleum diesel) on occupational and environmental exposures at a rural municipal facility in Keene, NH. For each fuel type, we measured concentrations of fine particulate matter (PM 2.5 ), elemental carbon (EC), and organic carbon (OC) at multiple locations (in-cabin, work area, and near-field) at a materials recovery facility utilizing non-road equipment. B20 fuel use resulted in significant reductions in PM 2.5 mass (56-76%), reductions in EC (5-29%), and increases in OC (294-467%). Concentrations of PM 2.5 measured during petroleum diesel use were up to four times higher than PM 2.5 concentrations during B20 use. Further analysis of the EC and OC fractions of total carbon also indicated substantial differences between fuels. Our results demonstrate that biodiesel blends significantly reduced PM 2.5 exposure compared to petroleum diesel fuel in a workplace utilizing non-road construction-type equipment. While this suggests that biodiesel may reduce health risks associated with exposure to fine particulate matter mass, more exposure research is needed to better understand biodiesel-related changes in particulate matter composition and other exposure metrics.