title: K-ras mutations in lung tumors from NNK-treated mice with lipopolysaccharide-elicited lung inflammation.
abstract: BACKGROUND
  Chronic lung inflammation has been associated with an increased risk of lung cancer. However, it is unclear whether such an event affects the incidence of mutations in the K-ras oncogene frequently found in lung tumors and suggested to be involved in lung tumorigenesis. This study investigated potential impacts of inflammation on the incidence of lung tumors and K-ras mutations using a mouse model.
  
  
  METHODS
  FVB/N mice were treated with lipopolysaccharide (LPS) for 16 weeks with or without co-treatment with 4-(methyl-nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) during the first 4 weeks.
  
  
  RESULTS
  There was a significant increase in lung inflammatory responses in mice treated with LPS and with LPS+NNK, compared with mice treated with NNK or with vehicle. The average number of lung tumors per mouse was 3.87 (between 1 and 6) and 0.73 (between 0 and 3) in mice treated with LPS+NNK and NNK alone, respectively (p<0.0001). No lung tumors were observed in mice treated with LPS or vehicle. A higher proportion of lung tumors from mice treated with LPS+NNK had K-ras mutations, compared with the mice treated with NNK alone (81.03% versus 45.45%, p<0.05).
  
  
  CONCLUSIONS
  LPS-elicited chronic lung inflammation significantly increases the risk of NNK-mediated lung tumorigenesis in FVB/N mice through K-ras gene activation by point mutations.
authors.affiliation: Environmental and Occupational Health, University of Pittsburgh, 100 Technology Drive, Bridgeside Point, Pittsburgh, PA 15219-3130, USA. pho1@pitt.edu
authors.forename: Phouthone
authors.initials: P
authors.lastname: Keohavong
authors.forename: Beth
authors.initials: B
authors.lastname: Kahkonen
authors.forename: Edwina
authors.initials: E
authors.lastname: Kinchington
authors.forename: Jinling
authors.initials: J
authors.lastname: Yin
authors.forename: Jide
authors.initials: J
authors.lastname: Jin
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: Y Peter
authors.initials: YP
authors.lastname: DI
mesh_terms: D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid; D017931:DNA Primers; D011905:Genes, ras; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics; D051379:Mice; D009154:Mutation; D009602:Nitrosamines / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D008070:Lipopolysaccharides; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone