Previously, we found strain dependent differences in the degree and resolution of the lung response in tumor susceptible (A/J) and resistant (C57BL/6J) mice exposed by pharyngeal aspiration to stainless steel (SS) welding fumes. We also found a borderline significant tumorigenic effect of gas metal arc (GMA)-SS fume. In this study, our objective was to further examine the inflammatory and potential carcinogenic effects of GMA-SS fume in mice via an inhalation exposure route. Male A/J and C57BL/6J mice were exposed to GMA-SS welding fume (40 mg/m3 x 3 hr/day x 6 or 10 days) or filtered air. At day 1, 4, 7, 10, 14 and 28 after the last exposure day, bronchoalveolar lavage (BAL) was done postmortem. Lung cytotoxicity (lactate dehydrogenase activity), air-blood barrier damage (albumin), inflammatory cytokines (IFN-y, IL-6, IL-10, IL-12p70, MCP-1, MIP-2, TNF-alpha), total BAL cell counts and differentials (.300 cells identified) were analyzed. Gross tumor counts and sizes were assessed in A/J mice at 78 weeks post-exposure. In both strains, inhalation of SS fume caused significant cytotoxicity and damage at all time points compared to air. Also, an early sustained macrophage and lymphocyte influx was found followed by a gradual neutrophil accumulation with no resolution of the response at 28 days post-exposure. MCP-1, MIP-2 and TNF-á were increased in both strains while the C57BL/6J also had increased IL-6 BAL protein. Tumor incidence and multiplicity in the 6 and 10 day GMA-SS-exposed groups were not significantly different from the corresponding air control groups. Furthermore, no tumor size differences were found in this study. Overall, inhalation of GMA-SS welding fume caused a similar lung inflammatory response in both mouse strains that was unresolved at 28 days post-exposure. Additionally, under the experimental conditions, GMA-SS welding fume did not significantly affect tumor development in A/J mice.
Biological-effects; Carcinogenicity; Cell-biology; Cell-damage; Cellular-reactions; Cytotoxic-effects; Exposure-assessment; Exposure-levels; Exposure-methods; Fumes; Gas-sampling; Gas-welders; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-cells; Lung-function; Pulmonary-cancer; Pulmonary-system-disorders; Respiratory-irritants; Statistical-analysis; Toxic-effects; Welders-lung
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah