Previous data from our laboratory showed a greater lung inflammatory response in tumor susceptible (A/J) versus resistant (C57BL/6J) mice to aspirated chromium containing manual metal arc-stainless steel welding fume (WF) at 7 and 28 days post-exposure. To gain further insight into the mechanisms and time course underlying this inflammatory response to WF, an acute time point was completed. Mice were exposed by pharyngeal aspiration to four doses (one dose every three days), of 5mg/kg WF, 1.5mg/kg soluble chromium (S-Cr), or saline vehicle. Bronchoalveolar lavage (BAL) and histopathology were done 2 days after the fourth dose. Lung injury (lactate dehydrogenase [LDH] and albumin), cytokines (IFN-ã, IL-6, MCP-1, and TNF-á), inflammatory cell influx (% polymorphonuclear leukocytes [PMN] and lymphocytes), and nitric oxide (NO) were measured in the BAL. At 2 days, both strains had increased lung injury, cytokines, and % PMN following exposure to WF or S-Cr but only the WF-exposed A/J mice had significantly increased NO levels. The C57BL/6J had equal degrees of inflammatory cell influx, lung injury, and cytokines following exposure to either WF or S-Cr. In contrast, the A/J mice exhibited a more heightened response to WF than to S-Cr, which was significantly higher than the C57BL/6J. Lung lesions, observed by histopathology, ranging from multifocal, minimal to moderate in severity, were found to be similar between the two strains and the exposure groups. It was also observed that the exposed C57BL/6J mice had higher lymphocyte numbers compared to the susceptible A/J strain. In conclusion, the mechanisms responsible for the lung inflammatory response to WF versus S-Cr appear to differ in the A/J but not in the C57BL/6J mice. These data suggest components, other than chromium, in the stainless steel WF exert additional toxicological effects in the A/J strain.
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina