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Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.

ABSTRACT: BACKGROUND: Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level. METHODS: Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. RESULTS: Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9. CONCLUSIONS: Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.

SUBMITTER: Zeidler-Erdely PC

PROVIDER: S-EPMC2892448 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.

Zeidler-Erdely Patti C PC Kashon Michael L ML Li Shengqiao S Antonini James M JM

Respiratory research 20100603

<h4>Background</h4>Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential ...[more]

PMID: 20525249

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Project description:BackgroundOccupational welding fumes contain varieties of toxic metal particles and may affect cardiovascular system like the Particulate Matters (PM). Few studies have focused on the effects of toxic metals on the hemodynamic balance; however, the reporting results were not consistent. This study aimed to investigate the association between toxic metals exposure (Chromium (Cr), Manganese (Mn) and Lead (Pb)) and blood hemostatic parameters status after a 3-week exposure cessation among workers exposed to welding fumes.MethodologyStructured interviews and biological samplings were conducted for 86 male workers without a history of Anemia and Cardiovascular diseases (CVDs) and working in a confined space to construct crude oil tanks. Metal levels of Cr, Mn and Pb in urine were measured during the working days using Inductively Coupled Plasma Mass Spectrometer (ICP-MS) method. The concentrations of hemostatic proteins in blood (White blood cell counts (WBC), Lymphocytes, Monocyte, Eosinophil, Neutrophil, Hematocrit (Hct) were assessed after a 3 weeks exposure cessation. Workers were divided into groups based on occupation type (welder group and non-welder group), and based on metal levels (high and low exposure groups) for comparison. Linear regression models were used to explore the association between metal exposure and multiple blood hemostatic parameters adjusted for age, Body Mass Index (BMI), and smoking status.ResultsUrine Mn and Cr level of the welder group was significantly higher than the non-welder group (Mn: 0.96 VS 0.22 ug/g creatinine, p < 0.001; Cr: 0.63 VS 0.22 ug/g creatinine, p < 0.01). The mean value of Hct in the welder group was 44.58 ± 2.84 vol%, significantly higher than the non-welder group (43.07 ± 3.31 vol%, p = 0.026). The median value of WBC in the high Mn-exposed group (6.93 ± 1.59 X 106 Cell/ml) was significantly lower than the low Mn-exposed group (7.90 ± 2.13 X 106 Cell/ml, p = 0.018). The linear regression analyses showed that there was a significantly negative association between log transformed WBC value and the Mn exposure groups (high and low) after adjusting for age, BMI, and smoking status (β = - 0.049, p = 0.045), but no significant result was found between WBC and occupation types (welder and non-welder) (p > 0.05). Multiple linear regression analysis also showed positive association between Hct and occupational types (welder and non-welders) (β = 0.014, p = 0.055). The other hemostatic parameters were not different from controls when divided by occupation type or metal level groups.ConclusionsOur results showed that welders were exposed to about 3 to 4 times higher Mn and Cr concentrations than non-welders. Moreover, one third of the non-welders were exposed to high-exposure groups of Mn and Cr metals. Regression models revealed a significant association of the WBC counts with the Mn exposure group. Therefore, we infer that Mn exposure may play a significant role on the blood hemostatic parameters of workers in the confined space. Hazard identification for non-welders should also be conducted in the confined space.

Project description:The welding of shear stud connectors to structural steel in construction requires a prolonged stooped posture that exposes ironworkers to biomechanical and welding fume hazards. In this study, biomechanical and welding fume exposures during stud welding using conventional methods were compared to exposures associated with use of a prototype system that allowed participants to weld from an upright position. The effect of base material (i.e. bare structural beam versus galvanized decking) on welding fume concentration (particle number and mass), particle size distribution, and particle composition was also explored. Thirty participants completed a series of stud welding simulations in a local apprenticeship training facility. Use of the upright system was associated with substantial reductions in trunk inclination and the activity levels of several muscle groups. Inhalable mass concentrations of welding fume (averaged over ~18 min) when using conventional methods were high (18.2 mg m(-3) for bare beam; 65.7 mg m(-3) for through deck), with estimated mass concentrations of iron (7.8 mg m(-3) for bare beam; 15.8 mg m(-3) for through deck), zinc (0.2 mg m(-3) for bare beam; 15.8 mg m(-3) for through deck), and manganese (0.9 mg m(-3) for bare beam; 1.5 mg m(-3) for through deck) often exceeding the American Conference of Governmental Industrial Hygienists Threshold Limit Values (TLVs). Number and mass concentrations were substantially reduced when using the upright system, although the total inhalable mass concentration remained above the TLV when welding through decking. The average diameters of the welding fume particles for both bare beam (31±17 nm) through deck conditions (34±34 nm) and the chemical composition of the particles indicated the presence of metallic nanoparticles. Stud welding exposes ironworkers to potentially high levels of biomechanical loading (primarily to the low back) and welding fume. The upright system used in this study improved exposure levels during stud welding simulations, but further development is needed before field deployment is possible.

Dataset Information

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.

Publications

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.

Similar Datasets

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