Abstract 4377: Pulmonary inflammation and lung tumorigenesis in mice

Chronic inflammation has been suggested to be associated with an increased risk of human cancer, including lung cancer, the leading cause of cancer death in the United States. However, the mechanisms of lung tumorigenesis associated with chronic lung inflammation still remain poorly understood. The purpose of this study is to get insight into the molecular mechanisms by which bacterial endotoxin-elicited chronic lung inflammation increases carcinogen-induced lung tumorigenesis. Groups of FBV/N mice were treated weekly for a 15-week period with lipopolysaccharide (LPS), a major pro-inflammatory glycolipid component of the gram-negative bacterial cell wall, with or without a co-treatment of 4-(methyl-nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), a major component of tobacco smoke and a potent lung carcinogen, during the first four weeks. Analysis of bronchoalveolar lavage fluid (BALF) at one day, one week, and fifteen weeks after LPS-treatment showed a significant increase in pro-inflammatory responses, including both in numbers of macrophages and inflammatory mediators in the mice treated with LPS alone and in those treated with LPS+NNK, compared with the mice treated with NNK alone or those treated with vehicles. These data were confirmed by pathological analysis and the presence of inflammatory cells and lung tissue injury from the groups of mice treated LPS or LPS+NNK, compared with those treated with NNK or vehicles. At week 15, the averaged number of lung tumors per mouse was 5.56 (100% tumor incidence; tumor numbers between 2-9) in mice treated with LPS+NNK and was significantly higher than 0.79 tumor per mouse (67% tumor incidence; tumor numbers between 0-2) in the mice treated with NNK alone (p