K-ras Mutations in Lung Tumors from NNK-treated Mice with Lipopolysaccharide-elicited Lung Inflammation

• Published in: Anticancer research Vol. 31; no. 9; pp. 2877 - 2882
• Main Authors: KEOHAVONG, Phouthone, KAHKONEN, Beth, KINCHINGTON, Edwina, JINLING YIN, JIDE JIN, XIAOPING LIU, SIEGFRIED, Jill M, PETER DI, Y
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-09-2011
• Subjects: Animals; Base Sequence; Biological and medical sciences; Bronchoalveolar Lavage Fluid; DNA Primers; Genes, ras; Lipopolysaccharides - pharmacology; Lung - drug effects; Lung - pathology; Lung Neoplasms - chemically induced; Lung Neoplasms - genetics; Medical sciences; Mice; Mutation; Nitrosamines - toxicity; Pneumology; Pneumonia - chemically induced; Polymerase Chain Reaction; Tumors; Tumors of the respiratory system and mediastinum; Lung cancer; Lung; Respiratory system; Carcinogenesis; K ras Gene; Cancerology; Lipopolysaccharide; Bronchus disease; Protooncogene; Lung disease; Respiratory disease; Nitrosamine; Rodentia; lung tumors; Inflammation; Malignant tumor; Carcinogen; Vertebrata; Mammalia; Treatment; Mouse; Animal; C-Onc gene; Mutation; Ras gene; K-ras mutations; Cancer; lung inflammation
• ISSN: 0250-7005; 1791-7530

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.
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.
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).
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.