Tumor promoter action of chromium-containing stainless steel welding particulate matter in the lungs of A/J mice.
Zeidler-Erdely-PC; Meighan-TG; Erdely-A; Battelli-LA; Kashon-ML; Keane-M; Antonini-JM
Toxicologist 2013 Mar; 132(1):237
Epidemiology studies show that occupational exposure to metal-rich welding particulate matter (PM) increases lung cancer risk. However, animal studies are lacking to conclusively link welding with an increased cancer risk. PM derived from stainless steel (SS) welding practices, in particular, contains carcinogenic metals such as hexavalent chromium and nickel. Previously, we found that PM derived from gas metal arc (GMA) welding of SS caused a borderline increase in lung tumor incidence and a significant, chronic immune response in the lungs of mice. Thus, we hypothesized that welding PM may act as a tumor promoter and increase lung tumor multiplicity. In this study, the capacity of GMA-SS welding PM to promote lung tumors was evaluated using a 2-stage (initiation-promotion) model in lung tumor susceptible A/J mice. Age and weight-matched male mice (n=26-29/group) were treated either with the initiator 3-methylcholanthrene (MCA;10 microg/g;i.p.) or vehicle (corn oil; CO) followed by 5 weekly pharyngeal aspirations of GMA-SS (340 or 680 microg) or PBS. Lung tumors were enumerated at 30 weeks following initiation with MCA. Body weights were recorded at 2 week intervals and no effect of treatment was found. MCA initiation followed by GMA-SS exposure promoted lung tumor multiplicity in both the lower dose (12.0 +/- 1.5 tumors/mouse; p=0.0001) and high dose (14.0 +/- 1.8 tumors/mouse; p=0.0001) groups significantly above that of MCA/PBS (4.77 +/- 0.7 tumors/mouse). Not only was this highly significant for the average total number per mouse, multiplicity was also increased (p<0.004) across all five individual lung regions of GMA-SS-exposed mice. No treatment effects were found in the corn oil groups at 30 weeks and also, as expected, tumor incidence was greater than 93% in the MCA treated groups which verified its carcinogenic potency. In conclusion, GMA-SS welding PM acts as a lung tumor promoter in vivo. These novel findings implicate that susceptible individuals may be at greater risk for lung cancer development after exposure to welding PM.
Toxicology; Laboratory-animals; Exposure-levels; Cancer; Pulmonary-disorders; Pulmonary-system; Lung-cancer; Dose-response; Carcinogens; Tumors; Lung-disorders; Cell-alteration; Methyl-compounds; Lung-cells; Cellular-reactions; Welders; Welders-lung; Welding; Welding-industry; Particulates; Metal-compounds; Stainless-steel; Work-practices; Hexavalent-chromium-compounds; Nickel-compounds; Gas-welders; Arc-welding; Arc-welders; Immune-reaction; In-vivo-study; Risk-factors
12597-68-1; 18540-29-9; 7440-02-0; 56-49-5
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas