Epidemiology studies suggest that inhalation of welding fume increases lung cancer risk in welders. Stainless steel (SS) fume, in particular, contains carcinogenic chromium and nickel. However, animal studies are lacking to conclusively link exposure to an increased lung cancer risk. An ongoing study in our laboratory has been to compare the inflammatory and tumorigenic responses to welding fume in lung tumor susceptible (A/J) and resistant (C57BL/6J) mice. Age and weight-matched male mice were exposed to gas metal arc-SS welding fume at 40mg/m3 x 3hr/d for 10 days. Control mice were exposed to filtered air. At 1, 4, and 7d after the final exposure, bronchoalveolar lavage (BAL) was done postmortem. Lung cytotoxicity (LDH activity), air-blood barrier damage (albumin), inflammatory cytokines (IFN-gamma, IL-6, IL-10, IL-12p70, MCP-1, TNF-alpha), total BAL cell counts, and differentials (>/=300 cells identified) were analyzed. Inhalation of SS fume caused significant cytotoxicity and damage at all time points in both strains. Air exposure caused no effect and BAL cells were >99% alveolar macrophages. In SS fume-exposed A/J mice, total cell numbers were increased 3.5, 5.6 and 7.6 fold compared to control at 1, 4, and 7d, respectively. The inflammatory response was dominated by an increasing neutrophilic component that reached 36% by 7d. A minor influx of macrophage/monocytes and lymphocytes (<2%) was found. No cytokines were increased at any time point in the A/J. In the C57BL/6J, total cells were increased 5.2 fold versus control and this increase was maintained among all time points. The response was dominated by macrophage/monocytes and lymphocytes (7-10%) with minimal neutrophils (<5%). MCP-1 and IL-6 were increased at all time points, which confirmed the cellular response in the C57BL/6J. In conclusion, the dissimilar responses to inhaled SS fume may be due to the genetic background of these strains. Chronic inhalation studies are planned to further evaluate these strain differences.
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington