Epidemiologic studies suggest an increased risk of
lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected "aged" gas
metal arc-
stainless steel (GMA-SS) welding fume has been shown by our laboratory to promote lung
tumor formation in vivo using a two-stage initiation-promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung
tumor promoter in lung
tumor-susceptible mice. Male A/J mice received intraperitoneal (IP)
injections of
corn oil or the chemical initiator
3-methylcholanthrene (MCA; 10 µg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS welding
aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m3. Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS fume significantly promoted lung
tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were
hyperplasias and
adenomas, which was consistent with developing lung
tumorigenesis.
Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS welding fume promotes lung
tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for
lung cancer.