Microarray Analysis of the Pulmonary Effects of Stainless and Mild Steel Welding Fumes in A/J and C57BL/6J Mice

Details

• Personal Author:
  Antonini JM ; Kashon ML ; Li S ; Zeidler-Erdely PC
• Description:
  Our earlier studies found supportive evidence for a tumorigenic effect of carcinogenic metal-containing welding fume in A/J mice. A/J mice are genetically predisposed to spontaneous and/or chemically-induced lung tumors while C57BL/6J (B6) mice are resistant. This genetic disparity provides a unique scenario to identify molecular mechanisms associated with the lung response to welding fume at the transcriptome level. Mice were exposed four times by pharyngeal aspiration to 5mg/kg mild steel (MS) fume, stainless steel (SS) fume, or saline vehicle. Mice were necropsied 28 days after the last exposure and whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. Ingenuity pathway analysis (cutoffs: p<0.05; fold change >1.3) of the microarray data revealed the top global molecular network involved in the A/J response to MS fume was behavior, nervous system development and function, and gene expression. In contrast, the connective tissue disorders, immunological disease, inflammatory disease network was most significant in the B6 strain. In the A/J, 75% of the focus molecules that met the cutoff were up-regulated as compared to 40% in the B6. Six genes were common between the strains such as KLF2, KLF4 and MARCO. SS fume exposure in the A/J induced genes primarily involved in connective tissue disorders, immunological disease, and inflammatory disease. Genes regulating cellular movement, hematological system development and function, and immune response were most involved in the B6 response. Of the significant focus molecules, 88% were up-regulated in the A/J compared to 45% in the B6. Only five common genes were found between the strains such as HSPH1, MMP12 and CTSK. Overall, these data confirm our previous observation that strain-dependent differences in response to welding fume occur in the A/J and B6 lung. Also, in contrast to the B6, the A/J strain exhibited a persistent up-regulation of welding fume-induced gene transcription suggesting that chronic lung cell activation may play a role in the tumorigenic effects of welding fume. [Description provided by NIOSH]
• Subjects:
  Biological Factors Carcinogens Environmental Monitoring Genetics Irritants Laboratories Lung Lung Diseases Metals Microbiology Occupational Health Particulate Matter Respiratory Function Tests Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety Welding

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• Keywords:
  Biological-effects Biological-factors Carcinogenesis Carcinogenicity Exposure-assessment Exposure-levels Exposure-methods Genetic-factors Inhalation-studies Laboratory-animals Lung-disorders Lung-function Lung-irritants Metal-fumes Microscopic-analysis Microscopy Particle-aerodynamics Particulate-dust Particulates Pulmonary-disorders Pulmonary-function-tests Pulmonary-system-disorders Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders Statistical-analysis Welders-lung Welding-industry

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035288
• Citation:
  Toxicologist 2009 Mar; 108(1):325
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f9c35cf4a3ae7d1a8ec7f12ad03294565d1eb3aac359fb82683efd7c1340c8b76eeb4619aa0511be1b22ca528edecb3faaf4acf186a5b9af3849897d3a5733a7
• Download URL:
  https://stacks.cdc.gov/view/cdc/187196/cdc_187196_DS1.pdf
• File Type:
  [PDF - 1.58 MB ]