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Welding Fume Exposure and Associated Inflammatory and Hyperplastic Changes in the Lungs of Tumor Susceptible A/J MiceHealth Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA Correspondence: Address correspondence to: James M. Antonini, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S 2015) Morgantown, WV 26505, USA; e-mail:jga6{at}cdc.gov
It has been suggested that welding fume (WF) exposure increases lung cancer risk in welders. Epidemiology studies have failed to conclude that WF alone causes lung cancer and animal studies are lacking. We examined the course of inflammation, damage, and repair in the lungs of A/J mice, a lung tumor susceptible strain, caused by stainless steel WF. Mice were exposed by pharyngeal aspiration to 40 mg/kg of WF, silica, or saline. Bronchoalveolar lavage (BAL) was performed 24 hours, 1 and 16 weeks to assess lung injury and inflammation and histopathology was done 1, 8, 16, 24, and 48 weeks postexposure. Both exposures increased inflammatory cells, lactate dehydrogenase and albumin at 24 hr and 1 week. At 16 weeks, these parameters remained elevated in silica-exposed but not WF-exposed mice. Histopathologic evaluation at 1 week indicated that WF induced bronchiolar epithelial hyperplasia with associated cellular atypia, alveolar bronchiolo-alveolar hyperplasia (BAH) in peribronchiolar alveoli, and peribronchiolar lymphogranulomatous inflammation. Persistent changes included foci of histiocytic inflammation, fibrosis, atypical bronchiolar epithelial cells, and bronchiolar BAH. The principle changes in silica-exposed mice were histiocytic and suppurative inflammation, fibrosis, and alveolar BAH. Our findings that WF causes persistent bronchiolar and peribronchiolar epithelial changes, suggest a need for studies of bronchiolar changes after WF exposure.
Key Words: bronchoalveolar hyperplasia • lung inflammation • silica • strain A mice • welding fume Abbreviations: ANOVA, analysis of variance • BAL, bronchoalveolar lavage • BAH, bronchiolo-alveolar hyperplasia • Cr, chromium • GMA- MS, gas metal arc-mild steel • GMA- SS, gas metal arc-stainless steel • H&E, hematoxylin and eosin • LDH, lactate dehydrogenase • MMA- SS, manual metal arc-stainless steel • Ni, nickel • PBS, phosphate-buffered saline • SE, standard error • WF, welding fume
Toxicologic Pathology, Vol. 34, No. 4,
364-372 (2006) |
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