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

Zeidler-Erdely, Patti C.; Kashon, Michael L.; Battelli, Lori; Young, Shih‐Houng; Erdely, Aaron; Roberts, Jenny R.; Reynolds, Steven H.; Antonini, James M.

doi:10.1186/1743-8977-5-12

Cited by 47 publications

(53 citation statements)

References 41 publications

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“…Regardless, the persistent inflammatory cytokine levels in the BAL up to 28 days after exposure confirmed that the lung response to inhaled welding fume increases incrementally over time in both mouse strains. These results contrast with aspiration and instillation exposure responses to welding fume (Antonini et al, 1996;Taylor et al, 2003;Zeidler-Erdely et al, 2008).…”

Section: Discussioncontrasting

confidence: 83%

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

Zeidler-Erdely¹,

Battelli²,

Stone³

et al. 2011

Inhalation Toxicology

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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. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice.

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Section: Discussioncontrasting

confidence: 83%

“…Our aspiration protocol delivered four bolus doses (85 μg/exposure) of GMA-SS welding fume over a 10-day time period (~340 μg total; Zeidler-Erdely et al, 2008). In this study, inhalation exposure deposited ~12 μg per day (~120 μg total) over 10 days.…”

Section: Discussionmentioning

confidence: 99%

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

Zeidler-Erdely¹,

Battelli²,

Stone³

et al. 2011

Inhalation Toxicology

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“…Moreover, it is important to underline that mediators such as TNF-α and IL-1ß, highly secreted by macrophages in response to NP (Figure 4), could also participate in the perpetuation of inflammation initiated by NP exposure since they have been shown to further induce the expression of chemotactic cytokines such as CCL-2, −3 and CXCL-2, thus sustaining the pulmonary increases of neutrophils, lymphocytes, and macrophages [32,35,36]. Similar events have been described in BAL fluid from animals exposed to welding fumes or other dusts [5,13,37-42]. These events could happen in welders, given that we were able to detect some of these cytokines in lung tissue sections of the patients analyzed in our study.…”

Section: Discussionmentioning

confidence: 74%

Role of metal oxide nanoparticles in histopathological changes observed in the lung of welders

et al. 2014

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BackgroundAlthough major concerns exist regarding the potential consequences of human exposure to nanoparticles (NP), no human toxicological data is currently available. To address this issue, we took welders, who present various adverse respiratory outcomes, as a model population of occupational exposure to NP.The aim of this study was to evaluate if welding fume-issued NP could be responsible, at least partially, in the lung alterations observed in welders.MethodsA combination of imaging and material science techniques including ((scanning) transmission electron microscopy ((S)TEM), energy dispersive X-ray (EDX), and X-ray microfluorescence (μXRF)), was used to characterize NP content in lung tissue from 21 welders and 21 matched control patients. Representative NP were synthesized, and their effects on macrophage inflammatory secretome and migration were evaluated, together with the effect of this macrophage inflammatory secretome on human lung primary fibroblasts differentiation.ResultsWelding-related NP (Fe, Mn, Cr oxides essentially) were identified in lung tissue sections from welders, in macrophages present in the alveolar lumen and in fibrous regions. In vitro macrophage exposure to representative NP (Fe2O3, Fe3O4, MnFe2O4 and CrOOH) induced the production of a pro-inflammatory secretome (increased production of CXCL-8, IL-1ß, TNF-α, CCL-2, −3, −4, and to a lesser extent IL-6, CCL-7 and −22), and all but Fe3O4 NP induce an increased migration of macrophages (Boyden chamber). There was no effect of NP-exposed macrophage secretome on human primary lung fibroblasts differentiation.ConclusionsAltogether, the data reported here strongly suggest that welding-related NP could be responsible, at least in part, for the pulmonary inflammation observed in welders. These results provide therefore the first evidence of a link between human exposure to NP and long-term pulmonary effects.

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“…Recent animal studies with MMA-and GMA-generated fumes indicate these to be weak lung tumor initiators in A/J mice, a lung tumor susceptible mouse strain. However, a chronic lung inflammatory response to these fumes was found, which may suggest that long-term exposure could increase lung tumor incidence and/or multiplicity in the A/J model (Solano-Lopez et al, 2006;Zeidler-Erdely et al, 2008.…”

Section: Welding Exposure and Health Effectsmentioning

confidence: 96%

“…In addition, a cellular influx consisting of alveolar macrophages (AM), neutrophils, lymphocytes, and, to a lesser extent, eosinophils was reported. Studies in both rats and mice that directly compared different types of welding fumes showed that SS fumes induced more lung toxicity as compared to MS fumes, an effect likely attributable to the greater proportion of toxic metals, such as Cr (Taylor et al, 2003;Zeidler-Erdely et al, 2008;Erdely et al, 2011b).…”

Section: Animal Immunotoxicity Studiesmentioning

confidence: 99%

Immunotoxicology of arc welding fume: Worker and experimental animal studies

Zeidler-Erdely

Erdely

Antonini

2012

Journal of Immunotoxicology

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

Abstract: The increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain.

Cited by 47 publications

References 41 publications

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

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

Role of metal oxide nanoparticles in histopathological changes observed in the lung of welders

Immunotoxicology of arc welding fume: Worker and experimental animal studies

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