Pulmonary inflammation and tumor induction in lung tumor susceptible A/J and resistant C57BL/6J mice exposed to welding fume.
BACKGROUND
Welding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 mug of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.5 mug soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure.


RESULTS
BAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the fumes. At 48 weeks, carcinogenic metal-containing GMA-SS fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this fume in lung cells compared to the other welding fumes was found.


CONCLUSIONS
The increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain.
Zeidler-Erdely
Patti C
PC
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, USA. paz9@cdc.gov.
Kashon
Michael L
ML
Battelli
Lori A
LA
Young
Shih-Houng
SH
Erdely
Aaron
A
Roberts
Jenny R
JR
Reynolds
Steven H
SH
Antonini
James M
JM
Scand J Work Environ Health. 2007 Oct;33(5):379-86
17973064
J Natl Cancer Inst. 1987 Apr;78(4):743-9
3470549
Respir Res. 2000;1(3):163-9
11667981
Anticancer Res. 2001 May-Jun;21(3B):1749-55
11497255
Toxicol Lett. 1998 Sep 1;98(1-2):77-86
9776564
Inhal Toxicol. 2004 Jan;16(1):27-32
14744662
Am Rev Respir Dis. 1991 May;143(5 Pt 1):1134-48
2024826
Crit Rev Toxicol. 2003;33(1):61-103
12585507
Toxicol Pathol. 1991;19(2):168-75
1771369
Scand J Work Environ Health. 2002 Jun;28(3):163-7
12109555
Carcinogenesis. 1997 Oct;18(10):1917-20
9364000
Mutat Res. 1978 Jan;56(3):235-43
342941
Scand J Work Environ Health. 1997 Apr;23(2):104-13
9167233
J Immunol Methods. 2008 Feb 29;331(1-2):59-68
18089291
Exp Pathol. 1986;30(3):129-41
3792485
Genes Dev. 2005 Mar 15;19(6):643-64
15769940
Carcinogenesis. 1997 Mar;18(3):531-7
9067553
J Toxicol Environ Health A. 1999 Nov 26;58(6):343-63
10580758
Toxicol Appl Pharmacol. 1996 Sep;140(1):188-99
8806885
J Natl Cancer Inst. 1999 Apr 21;91(8):675-90
10218505
Cancer Res. 2004 Apr 1;64(7):2307-16
15059877
Int J Occup Environ Health. 1998 Apr-Jun;4(2):85-8
10026469
Carcinogenesis. 2000 Apr;21(4):533-41
10753182
Am J Ind Med. 1996 Oct;30(4):383-91
8892542
Toxicol Sci. 2004 Sep;81(1):26-34
15159525
Curr Med Chem. 2007;14(12):1279-89
17504213
J Natl Cancer Inst. 1985 Nov;75(5):963-9
3863993
Toxicol Appl Pharmacol. 2007 Sep 15;223(3):234-45
17706736
Toxicol Sci. 2003 Sep;75(1):181-91
12832661
Exp Lung Res. 1991 Mar-Apr;17(2):157-68
2050022
Cancer Res. 1992 Jun 1;52(11):3164-73
1591728
Exp Lung Res. 1998 Jul-Aug;24(4):541-55
9659582
Toxicol Pathol. 2006;34(4):364-72
16844664
Adv Cancer Res. 1975;21:1-58
1108612
Scand J Work Environ Health. 1977 Dec;3(4):203-11
339336
Toxicol Pathol. 1989;17(4 Pt 2):737-42
2483278
J Occup Environ Hyg. 2006 Apr;3(4):194-203; quiz D45
16531292
Toxicol Lett. 1982 Apr;11(1-2):159-63
6896394
Methods. 2001 Dec;25(4):402-8
11846609
Mol Cell Biochem. 2005 Nov;279(1-2):17-23
16283511
Cancer Res. 1996 May 1;56(9):2224-8
8616876
IARC Monogr Eval Carcinog Risks Hum. 1990;49:1-648
2232124
Int J Radiat Biol. 1997 Mar;71(3):301-8
9134020
Cancer Res. 2000 Sep 15;60(18):5017-20
11016621
J Toxicol Environ Health A. 2003 Aug 8;66(15):1441-52
12857634