Reactive oxygen species-induced DNA effects of peripheral blood mononuclear cells isolated from rats after pulmonary exposure to welding fume

Details

• Personal Author:
  Antonini JM ; Erdely A ; Eye T ; Farris B ; Kodali V ; Meighan T ; Roberts, Jennifer R. ; Salmen R ; Shoeb M ; Zeidler-Erdely PC
• Description:
  Welding fume is a complex mixture of different potentially cytotoxic and genotoxic metals, such as Cr, Mn, Ni, and Fe. The pulmonary effects of welding fume have been well-described; however, less is known about the extra-pulmonary responses. The objective of the study was to assess the systemic effects of welding fume by examining molecular and cellular changes of isolated peripheral blood mononuclear cells (PBMC) in a rat model. Male Sprague-Dawley rats were treated by intratracheal instillation (IT) with 2.0 mg/rat of gas metal arc-mild steel (GMA-MS) and manual metal arc-stainless steel (MMA-SS) welding fume. Vehicle controls received sterile saline by IT. At 4 h, 14 h, 72 h, and 10 d, bronchoalveolar lavage (BAL) was performed to assess lung toxicity. Whole blood was collected, PBMC were isolated, and the production of reactive oxygen species (ROS) and DNA alterations in PBMC were assessed by measuring 4-hydroxylnonenal protein adduct (P-HNE) formation using fluorescence microscopy and DNA methylation and telomere length, respectively. Metal composition of the two fumes was different: MMA-SS (41% Fe, 29% Cr, 17% Mn, 3% Ni) versus GMA-MS (85% Fe, 14% Mn). BAL indicators of lung injury and inflammation were increased with MMA-SS treatment compared to other exposures at 14 h, 72 h, and 10 d after treatment. ROS generation and P-HNE adduct formation increased at 14 h in the PBMC recovered from the MMA-SS group compared to other groups. Furthermore, an increase in DNA methylation in PBMC was measured as early as 4 h after MMA-SS treatment, whereas variable responses in telomere length were observed when comparing the groups at the different time points. These findings suggest that genotoxic metals in MMA-SS fume (e.g., Cr and Ni), that are absent in the GMA-MS fume, may enhance lung toxicity, as well as generation of oxidative- stress markers and DNA alterations in PBMC. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Animals Blood Environmental Exposure Hazardous Substances Hematologic Tests Immune System Inhalation Exposure Laboratories Lung Metals Microbiology Occupational Health Respiratory System Safety Toxicology Welding

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• Keywords:
  Arc Welding Blood Cells Blood Samples Cell Alteration DNA Damage Exposure Assessment Exposure Levels Immune Reaction Inhalants Laboratory Animals Laboratory Testing Lung Function Metal Compounds Microscopic Analysis Oxidative Stress Pulmonary Effects Pulmonary Function Reactive Oxygen Species ROS Stainless Steel Toxic Effects Toxic Fumes Welders Lung Welding Fumes

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  68
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047606
• Citation:
  Toxicologist 2016 Mar; 150(1):68
• CAS Registry Number:
  Chromium (CAS RN 7440-47-3) ; Iron (CAS RN 7439-89-6) ; Manganese (CAS RN 7439-96-5) ; Nickel (CAS RN 7440-02-0) ; Stainless Steel (CAS RN 12597-68-1)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:22109f0700b814a9aeaee28e58c2d7e9b8508fad3617b0b8ca93a2189c022b76648f23e5a282a2be716e373764db5ac84c65ac465ccce93301ecd038c04a4682
• Download URL:
  https://stacks.cdc.gov/view/cdc/202621/cdc_202621_DS1.pdf
• File Type:
  [PDF - 442.29 KB ]