title: Inhalation of gas metal arc-stainless steel welding fume promotes lung tumorigenesis in A/J mice.
abstract: 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.
authors.affiliation: West Virginia University, School of Medicine, Morgantown, WV, USA.|Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Lauryn M
authors.initials: LM
authors.lastname: Falcone
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Erdely
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Terence G
authors.initials: TG
authors.lastname: Meighan
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Battelli
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Salmen
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: McKinney
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Stone
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Cumpston
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Cumpston
authors.affiliation: Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Cincinnati, OH, USA.
authors.forename: Ronnee N
authors.initials: RN
authors.lastname: Andrews
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kashon
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road (M/S L2015), Morgantown, WV, 26505, USA. paz9@cdc.gov.
authors.forename: Patti C
authors.initials: PC
authors.lastname: Zeidler-Erdely
mesh_terms: D000280:Administration, Inhalation; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D019570:Inhalation Exposure / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008748:Methylcholanthrene / Q000008:administration & dosage; D051379:Mice; D008815:Mice, Inbred Strains; D009784:Occupational Diseases / Q000209:etiology / Q000473:pathology; D016273:Occupational Exposure / Q000009:adverse effects; D013193:Stainless Steel / Q000633:toxicity; D014896:Welding
chemical_list: D000395:Air Pollutants, Occupational; D013193:Stainless Steel; D008748:Methylcholanthrene
keywords: A/J mouse; Cancer; Inhalation; Stainless steel; Welding