Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner.
BACKGROUND
Elevated levels of air pollution are associated with increased risk of lung cancer. Particulate matter (PM) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation, a lung cancer risk factor. Vanadium pentoxide (V2O5) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans. In the current investigation we examined the influence of genetic background on susceptibility to V2O5-induced inflammation and evaluated whether V2O5 functions as a tumor promoter using a 2-stage (initiation-promotion) model of pulmonary neoplasia in mice.


RESULTS
A/J, BALB/cJ (BALB), and C57BL/6J (B6) mice were treated either with the initiator 3-methylcholanthrene (MCA; 10 microg/g; i.p.) or corn oil followed by 5 weekly aspirations of V2O5 or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment. Susceptibility to V2O5-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid (BALF), and chemokines, transcription factor activity, and MAPK signaling were quantified in lung homogenates. We found that treatment of animals with MCA followed by V2O5 promoted lung tumors in both A/J (10.3 +/- 0.9 tumors/mouse) and BALB (2.2 +/- 0.36) mice significantly above that observed with MCA/PBS or V2O5 alone (P < 0.05). No tumors were observed in the B6 mice in any of the experimental groups. Mice sensitive to tumor promotion by V2O5 were also found to be more susceptible to V2O5-induced pulmonary inflammation and hyperpermeability (A/J>BALB>B6). Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1, higher NFkappaB and c-Fos binding activity, as well as sustained ERK1/2 activation in lung tissue.


CONCLUSIONS
In this study we demonstrate that V2O5, an occupational and environmentally relevant metal oxide, functions as an in vivo lung tumor promoter among different inbred strains of mice. Further, we identified a positive relationship between tumor promotion and susceptibility to V2O5-induced pulmonary inflammation. These findings suggest that repeated exposures to V2O5 containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways.
Rondini
Elizabeth A
EA
Department of Pathobiology and Diagnostic Investigation and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
Walters
Dianne M
DM
Bauer
Alison K
AK
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D019570:Inhalation Exposure; D055370:Lung Injury / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics; D008807:Mice, Inbred BALB C / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism; D017968:Vanadium Compounds / Q000633:toxicity*
D000393:Air Pollutants; D002273:Carcinogens; D018925:Chemokines; D014157:Transcription Factors; D017968:Vanadium Compounds; D008748:Methylcholanthrene; C066075:vanadium pentoxide
Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 1):669-74
7881654
Inflammation. 2000 Dec;24(6):505-17
11128049
Chest. 2002 Jun;121(6):2052-60
12065377
Carcinogenesis. 1999 Apr;20(4):663-8
10223197
Arch Environ Health. 1967 Dec;15(6):728-38
6075124
J Immunol. 2008 Mar 15;180(6):4200-7
18322232
Carcinogenesis. 2002 Mar;23(3):411-7
11895855
Cancer Lett. 2003 Aug 20;198(2):139-44
12957351
Cancer Cell. 2004 Nov;6(5):447-58
15542429
Biochem Biophys Res Commun. 1992 Apr 30;184(2):922-9
1374243
J Biol Chem. 2002 Jan 18;277(3):1837-44
11706017
Toxicol Sci. 2003 Aug;74(2):287-96
12773761
Crit Rev Oncol Hematol. 2002 Apr;42(1):93-103
11923071
Cancer Res. 1994 Jan 1;54(1):36-40
8261458
Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L685-703
15355860
J Appl Physiol (1985). 2001 Mar;90(3):1111-7
11181627
J Toxicol Environ Health A. 2005 Jul 9-23;68(13-14):1301-7
16024504
Am J Ind Med. 1999 Apr;35(4):366-74
10086213
J Natl Cancer Inst. 2006 May 17;98(10):691-9
16705123
JAMA. 2002 Mar 6;287(9):1132-41
11879110
Environ Health Perspect. 1997 Sep;105 Suppl 5:1053-60
9400700
Toxicol Appl Pharmacol. 1999 May 1;156(3):170-8
10222309
IARC Monogr Eval Carcinog Risks Hum. 2006;86:1-294
16906675
Carcinogenesis. 2002 Oct;23(10):1737-43
12376484
Cancer Immunol Immunother. 2000 May;49(2):63-70
10823415
Am J Respir Crit Care Med. 2002 Jun 15;165(12):1610-7
12070061
Cancer Res. 2007 May 15;67(10):4933-9
17510423
Environ Health Perspect. 2004 Nov;112(15):1447-59
15531427
Chem Res Toxicol. 1997 Oct;10(10):1104-8
9348432
Oncogene. 2007 May 14;26(22):3291-310
17496923
N Engl J Med. 1993 Dec 9;329(24):1753-9
8179653
Vet Pathol. 2009 May;46(3):369-90
19176494
Am J Respir Cell Mol Biol. 2002 Feb;26(2):175-82
11804867
Pulm Pharmacol Ther. 2007;20(5):596-605
16919984
J Biol Chem. 1999 Jul 16;274(29):20307-12
10400652
Am J Respir Cell Mol Biol. 1999 Sep;21(3):357-64
10460753
Toxicol Appl Pharmacol. 1997 Oct;146(2):180-8
9344885
Eur J Biochem. 1997 Jan 15;243(1-2):49-57
9030721
J Toxicol Environ Health. 1997 Feb 21;50(3):285-305
9055877
J Natl Cancer Inst. 2005 Dec 7;97(23):1778-81
16333033
Expert Rev Anticancer Ther. 2008 Apr;8(4):605-15
18402527
Respir Res. 2010 Feb 25;11:24
20184723
Am J Ind Med. 2001 May;39(5):454-62
11333407
Br J Cancer. 2004 Nov 29;91(11):1970-6
15545974
Radiat Res. 2007 Jun;167(6):711-26
17523851
Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57
1751545
Int J Oncol. 1998 Oct;13(4):711-5
9735400
Exp Lung Res. 2001 Apr-May;27(3):197-216
11293324
Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L209-16
10645909
Am J Physiol Lung Cell Mol Physiol. 2003 May;284(5):L774-82
12676768
Am J Physiol. 1998 Sep;275(3):L551-8
9728050
Free Radic Biol Med. 2003 Oct 15;35(8):845-55
14556849
Environ Health Perspect. 2008 Dec;116(12):1689-93
19079721
Oncogene. 2006 Mar 30;25(14):2105-12
16288213
Am J Pathol. 2002 Aug;161(2):459-70
12163371
Nature. 2002 Dec 19-26;420(6917):860-7
12490959
Toxicol Appl Pharmacol. 1996 May;138(1):1-11
8658498
Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1340-3
15894700
Nat Rev Cancer. 2006 Jan;6(1):24-37
16397525
J Pathol. 2000 Apr;190(5):619-26
10727989
J Immunol. 2004 Mar 1;172(5):2853-60
14978086
PLoS One. 2008;3(12):e3879
19060952
Oncogene. 1996 Oct 17;13(8):1599-604
8895504
Genomics. 1998 Oct 15;53(2):129-36
9790761
Am J Respir Cell Mol Biol. 2000 Oct;23(4):537-45
11017920
Toxicology. 2001 Dec 1;169(1):1-15
11696405
Cancer Res. 2006 Apr 15;66(8):4198-207
16618742
Cell Biol Toxicol. 1990 Jul;6(3):303-14
2253055
J Exp Med. 1989 Apr 1;169(4):1485-90
2926331
Toxicol Pathol. 2007 Jan;35(1):148-53
17325983
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18514-9
18000061
Int J Cancer. 2004 May 10;109(6):799-809
15027112
Occup Environ Med. 1995 May;52(5):353-8
7795759
J Pharmacol Exp Ther. 2007 Aug;322(2):486-93
17496165
Lung Cancer. 2007 Apr;56(1):25-33
17175059
Am J Epidemiol. 1995 Jun 15;141(12):1161-9
7771454
Br J Ind Med. 1980 Nov;37(4):337-62
7004477
J Cell Physiol. 2003 Apr;195(1):99-107
12599213
Am Rev Respir Dis. 1985 Dec;132(6):1181-5
3907443
CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
17237035
Am J Respir Cell Mol Biol. 2000 May;22(5):590-6
10783131