Pulmonary toxicity and global gene expression changes in response to sub-chronic inhalation exposure to crystalline silica in rats.

Exposure to crystalline silica results in serious adverse health effects, most notably, silicosis. An understanding of the mechanism(s) underlying silica-induced pulmonary toxicity is critical for the intervention and/or prevention of its adverse health effects. Rats were exposed by inhalation to crystalline silica at a concentration of 15 mg/m, 6 hr/day, 5 days/week for 3, 6 or 12 weeks.

Molecular mechanisms of pulmonary response progression in crystalline silica exposed rats.

An understanding of the mechanisms underlying diseases is critical for their prevention. Excessive exposure to crystalline silica is a risk factor for silicosis, a potentially fatal pulmonary disease. Male Fischer 344 rats were exposed by inhalation to crystalline silica (15 mg/m, six hours/day, five days) and pulmonary response was determined at 44 weeks following termination of silica exposure.

Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically.

Interactive effects of cerium oxide and diesel exhaust nanoparticles on inducing pulmonary fibrosis.

Cerium compounds have been used as a fuel-borne catalyst to lower the generation of diesel exhaust particles (DEPs), but are emitted as cerium oxide nanoparticles (CeO2) along with DEP in the diesel exhaust. The present study investigates the effects of the combined exposure to DEP and CeO2 on the pulmonary system in a rat model. Specific pathogen-free male Sprague-Dawley rats were exposed to CeO2 and/or DEP via a single intratracheal instillation and were sacrificed at various time points post-exposure.

Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses.

Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL).

Lung toxicity and biodistribution of Cd/Se-ZnS quantum dots with different surface functional groups after pulmonary exposure in rats.

Background: The potential use of quantum dots (QD) in biomedical applications, as well as in other systems that take advantage of their unique physiochemical properties, has led to concern regarding their toxicity, potential systemic distribution, and biopersistence. In addition, little is known about workplace exposure to QD in research, manufacturing, or medical settings. The goal of the present study was to assess pulmonary toxicity, clearance, and biodistribution of QD with different functional groups in rats after pulmonary exposure.

Adjuvant effect of zymosan after pulmonary treatment in a mouse ovalbumin allergy model.

An association has been observed between indoor mold contamination and lung allergy and asthma. This relationship is not fully understood. 1→3-β-Glucan is the major cell wall component of fungi and a good marker of fungi exposure.

Transcriptomics analysis of lungs and peripheral blood of crystalline silica-exposed rats.

Minimally invasive approaches to detect/predict target organ toxicity have significant practical applications in occupational toxicology. The potential application of peripheral blood transcriptomics as a practical approach to study the mechanisms of silica-induced pulmonary toxicity was investigated. Rats were exposed by inhalation to crystalline silica (15 mg/m(3), 6 h/day, 5 days) and pulmonary toxicity and global gene expression profiles of lungs and peripheral blood were determined at 32 weeks following termination of exposure.

Oxidative stress and dermal toxicity of iron oxide nanoparticles in vitro.

A number of commercially available metal/metal oxide nanoparticles (NPs) such as superparamagnetic iron oxide (SPION) are utilized by the medical field for a wide variety of applications. These NPs may able to induce dermal toxicity via their physical nature and reactive surface properties. We hypothesize that SPION may be toxic to skin via the ability of particles to be internalized and thereby initiate oxidative stress, inducing redox-sensitive transcription factors affecting/leading to inflammation.

Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos.

Background: Carbon nanotubes (CNT) and carbon nanofibers (CNF) are allotropes of carbon featuring fibrous morphology. The dimensions and high aspect ratio of CNT and CNF have prompted the comparison with naturally occurring asbestos fibers which are known to be extremely pathogenic. While the toxicity and hazardous outcomes elicited by airborne exposure to single-walled CNT or asbestos have been widely reported, very limited data are currently available describing adverse effects of respirable CNF.

Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols.

Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations.

Single-Walled Carbon Nanotubes Induce Fibrogenic Effect by Disturbing Mitochondrial Oxidative Stress and Activating NF-κB Signaling.

Single-walled carbon nanotubes (SWCNTs) are newly discovered material of crystalline carbon that forms single-carbon layer cylinders with nanometer diameters and varying lengths. Although SWCNTs are potentially suitable for a range of novel applications, their extremely small size, fiber-like shape, large surface area, and unique surface chemistry raise potential hazard to humans, including lung toxicity and fibrosis. The molecular mechanisms by which SWCNTs cause lung damage remain elusive.

Multiwalled carbon nanotubes induce a fibrogenic response by stimulating reactive oxygen species production, activating NF-κB signaling, and promoting fibroblast-to-myofibroblast transformation.

Carbon nanotubes (CNTs) are novel materials with unique electronic and mechanical properties. The extremely small size, fiberlike shape, large surface area, and unique surface chemistry render their distinctive chemical and physical characteristics and raise potential hazards to humans. Several reports have shown that pulmonary exposure to CNTs caused inflammation and lung fibrosis in rodents.

Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein phosphorylation and substance P synthesis in nodose ganglia.

The inhalation of engineered nanoparticles stimulates the development of atherosclerosis and impairs vascular function. However, the cardiac effects of inhaled engineered nanoparticles are unknown. Here, we investigate the effects of ultrafine titanium dioxide (UFTiO(2)) on the heart, and we define the possible mechanisms underlying the measured effects.

Identification of systemic markers from a pulmonary carbon nanotube exposure.

Objective: Interest exists for early monitoring of worker exposure to engineered nanomaterials. Here, we highlight quantitative systemic markers of early effects after carbon nanotube (CNT) exposure.

Methods: Mice were exposed by pharyngeal aspiration to 40-μg CNT and harvested 24 hours, 7 days, and 28 days postexposure for measurements of whole blood, lung and extrapulmonary tissue gene expression, blood and bronchoalveolar lavage (BAL) differentials, and serum protein profiling.

Direct effects of carbon nanotubes on dendritic cells induce immune suppression upon pulmonary exposure.

Pharyngeal aspiration of single-walled carbon nanotubes (SWCNTs) caused inflammation, pulmonary damage, and an altered cytokine network in the lung. Local inflammatory response in vivo was accompanied by modified systemic immunity as documented by decreased proliferation of splenic T cells. Preincubation of naïve T cells in vitro with SWCNT-treated dendritic cells reduced proliferation of T cells.

Blood gene expression profiling detects silica exposure and toxicity.

Blood gene expression profiling was investigated as a minimally invasive surrogate approach to detect silica exposure and resulting pulmonary toxicity. Rats were exposed by inhalation to crystalline silica (15 mg/m³, 6 h/day, 5 days), and pulmonary damage and blood gene expression profiles were determined after latency periods (0-16 weeks). Silica exposure resulted in pulmonary toxicity as evidenced by histological and biochemical changes in the lungs.

Short-term inhalation of stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice.

Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) welding fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS welding fume at 40 mg/m(3)×3 h/day for 6 and 10 days.

Titanium dioxide (TiO2) nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways.

Titanium dioxide (TiO(2)), a commercially important material, is used in a wide variety of products. Although TiO(2) is generally regarded as nontoxic, the cytotoxicity, pathogenicity, and carcinogenicity of TiO(2) nanoparticles have been recently recognized. The present study investigated TiO(2) nanoparticle-induced cell apoptosis and molecular mechanisms involved in this process in a mouse epidermal (JB6) cell line.

Preexposure to repeated low doses of zymosan increases the susceptibility to pulmonary infection in rats.

Chronic exposure to low levels of mold has been reported to increase susceptibility to respiratory infections. In the current study, the authors investigate the lungs' ability to clear an infection after repeated low-dose zymosan exposure. Exposure was conducted at a zymosan dose of 0.

The soluble nickel component of residual oil fly ash alters pulmonary host defense in rats.

The soluble metal fraction of residual oil fly ash (ROFA) has been shown to increase the susceptibility to infection in animal models. The goal of this study was to determine which of the primary soluble metals or metal combinations in ROFA were responsible for the increased infectivity. The soluble fraction of ROFA contained Ni, Fe, Al, and Zn.

Single pre-exposure to a high dose of zymosan enhances lung defense mechanisms and accelerates the pulmonary clearance of a bacterial pathogen in rats.

The present study examines the effects of pre-exposure to zymosan (a 1 --> 3-beta-glucan from baker yeast) on lung defense against bacterial infection. Rats received a single dose of zymosan A (0.6, 1.

Pulmonary inflammation and tumor induction in lung tumor susceptible A/J and resistant C57BL/6J mice exposed to welding fume.

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 mug of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.

Performance evaluation of cytometric bead assays for the measurement of lung cytokines in two rodent models.

There is a growing demand for a cost-effective, efficient, and high-throughput method for measuring cytokines. Currently, many studies are using flow cytometric bead-based multiplex assays in the measurement of cytokines. However, limited data are available regarding the performance of these cytometric bead assays versus enzyme-linked immunosorbent assay (ELISA) or correlation with mRNA expression using real time reverse transcriptase-polymerase chain reaction (RT-PCR).