title: Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner.
abstract: 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.
authors.affiliation: Department of Pathobiology and Diagnostic Investigation and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rondini
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Walters
authors.forename: Alison K
authors.initials: AK
authors.lastname: Bauer
mesh_terms: 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*
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; D018925:Chemokines; D014157:Transcription Factors; D017968:Vanadium Compounds; D008748:Methylcholanthrene; C066075:vanadium pentoxide
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