Abstract
Welding fumes induce lung toxicity and are carcinogenic to humans but the molecular mechanisms have yet to be clarified. The aim of this study was to evaluate the toxicity of stainless and mild steel particles generated via gas–metal arc welding using primary human small airway epithelial cells (hSAEC) and ToxTracker reporter murine stem cells, which track activation of six cancer-related pathways. Metal content (Fe, Mn, Ni, Cr) of the particles was relatively homogenous across particle size. The particles were not cytotoxic in reporter stem cells but stainless steel particles activated the Nrf2-dependent oxidative stress pathway. In hSAEC, both particle types induced time- and dose-dependent cytotoxicity, and stainless steel particles also increased generation of reactive oxygen species. The cellular metal content was higher for hSAEC compared to the reporter stem cells exposed to the same nominal dose. This was, in part, related to differences in particle agglomeration/sedimentation in the different cell media. Overall, our study showed differences in cytotoxicity and activation of cancer-related pathways between stainless and mild steel welding particles. Moreover, our data emphasizes the need for careful assessment of the cellular dose when comparing studies using different in vitro models.
Highlights
Welding fumes induce lung toxicity and are carcinogenic to humans but the molecular mechanisms have yet to be clarified
The mild steel particles consisted mainly of Mn and Fe, while the stainless steel particles were enriched in Ni and Cr, as indicated by the aerosol mass spectrometry data
We performed a quantitative evaluation of the metals by particle induced X-ray emission (PIXE) at different stages: (i) metal electrodes (ii) different size fractions during particles during generation and (iii) collected particles after dispersion in water (Fig. 2 and Supplementary Fig. 1)
Summary
Welding fumes induce lung toxicity and are carcinogenic to humans but the molecular mechanisms have yet to be clarified. Exposure to welding fumes has been classified as carcinogenic to humans (class 1, IARC) based on a series of epidemiological studies that reported an increased risk of lung cancer among exposed w orkers[1]. In vitro studies reveal that stainless steel and mild steel welding particles are cytotoxic, increase the production of reactive oxygen species (ROS) and the release of proinflammatory cytokines (IL-1, IL-6, TNFα), and induce mitochondrial dysfunction as well as lipid p eroxidation[7, 8, 19, 20] These effects appear to be consistently more prominent in cells exposed to stainless steel particles compared with mild steel, a difference attributed to increased content and/or solubility of transition metals e.g. C r8, 20. The effects seen in cells exposed to mild steel seem to be correlated with the size of the particles with an increased effect after exposure to the fine and ultrafine fractions compared to coarse particles[7, 21]
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