Epidemiological studies examining the potential association of occupational inhalation of welding fumes and increased incidence of lung cancer have not reached definite conclusions. Stainless steel (SS) welding fumes are of particular interest because they contain potential human carcinogens, such as chromium and nickel. Animal studies addressing toxicological responses related to carcinogenicity are currently lacking, although SS welding fumes have been shown to be mutagenic in vitro. The goals of this study were to examine the potential for SS welding fumes to damage DNA and induce apoptosis, events that are associated with possible carcinogenic activity. In a previous study using electron spin resonance, the generation of hydroxyl radicals from Cr(VI) in the SS fume (1.0 mg/ml) was observed. In the current study, SS fume at the same concentration caused plasmid DNA strand breakage in vitro under similar conditions. To examine the effects of SS fumes on apoptosis in vivo, male Sprague-Dawley rats were intratracheally instilled with SS fumes from manual metal arc welding (La mg/100 g bw), Cr(VI) (0.2 mg/100 g bw) as a positive control, or the saline vehicle. On days 1, 3, 6, 8, and 10, the rats were euthanized and their left lungs were excised and cryo-sectioned. Apoptosis was examined in the tissue sections by TUNEL assay. Increased numbers of apoptotic cells were found in lung tissue treated with either the SS fume or the positive control, Cr(VI), as compared to lungs from saline-treated animals. These preliminary studies indicate that SS welding fumes can damage DNA in vitro and induce apoptosis in vivo. Studies are ongoing to determine if the apoptotic event is associated with an increase in oxidative DNA damage in lung tissue.
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland