8-oxo-7-8-dihydrodeoxyguanine and Pulmonary-Fibrosis

Welder's pneumoconiosis has generally been determined to be benign and unassociated with respiratory symptoms based on the absence of pulmonary-function abnormalities in welders with marked radiographic abnormalities. In previous studies, the current authors suggested a three-phase lung fibrosis process to study the pathological process of lung fibrosis and found that the critical point for recovery was after 30 days of welding-fume exposure at a high dose, at which point early and delicate fibrosis was observed in the perivascular and peribronchiolar regions. Accordingly, the current study investigated the inflammatory and genotoxic responses during a 30-day period of welding-fume exposure to elucidate the process of fibrosis. As such, rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes at concentrations of 65.6 +/- 2.9 (low dose) and 116.8 +/- 3.9 mg/m3 (high dose) total suspended particulate for 2 h per day in an inhalation chamber for 30 days. Animals were sacrificed after the initial 2 h exposure, and after 15 and 30 days of exposure. The rats exposed to the welding fumes exhibited a statistically significant (P < 0.05) decrease in body weight when compared to the control during the 30-day exposure period, yet an elevated cellular differential count and higher levels of albumin, LDH, and beta-NAG, but not elevated TNF-alpha, and IL-1beta in the acellular bronchoalveolar lavage fluid. In addition, the DNA damage resulting from 30 days of welding-fume exposure was confirmed by a comet assay and the inmmunohistochemistry for 8-hydroxydeoxyguanine (8-OH-dG). Consequently, the elevated inflammatory and genotoxic indicators confirmed the lung injury and inflammation caused by the MMA-SS welding-fume exposure.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylglucosaminidase; Air Pollutants, Occupational; Albumins; Animals; Body Weight; Bronchoalveolar Lavage Fluid; Comet Assay; DNA; DNA Damage; Dose-Response Relationship, Drug; Guanine; Inhalation Exposure; L-Lactate Dehydrogenase; Leukocyte Count; Lung; Macrophages, Alveolar; Male; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms; Stainless Steel; Welding