Cigarette smoke exposure increases ulcerative colitis-associated colonic adenoma formation in mice

• Published in: Carcinogenesis (New York) 2003-08, Vol.24 (8), p.1407-1413
• Main Authors: Liu, Edgar S.L., Ye, Yi-Ni, Shin, Vivian Y., Yuen, Siu-Tsan, Leung, Suet-Yi, Wong, Benjamin C.Y., Cho, Chi-Hin
• Format: Article
• Language: English
• Subjects: Adenoma - etiology; Adenoma - pathology; Animals; Apoptosis - drug effects; Biological and medical sciences; Blotting, Western; Carcinogenesis, carcinogens and anticarcinogens; Cell Division - drug effects; Cell Transformation, Neoplastic; Chemical agents; Chronic Disease; cigarette smoke; Colitis, Ulcerative - etiology; Colitis, Ulcerative - pathology; Colonic Neoplasms - etiology; Colonic Neoplasms - pathology; Dextran Sulfate - toxicity; dextran sulfate sodium; DSS; Endothelial Growth Factors - metabolism; Intercellular Signaling Peptides and Proteins - metabolism; Lymphokines - metabolism; Male; Medical sciences; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic - etiology; PCNA; proliferating cell nuclear antigen; Proto-Oncogene Proteins c-bcl-2 - metabolism; Smoking - adverse effects; Tobacco, tobacco smoking; Toxicology; Tumors; vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; VEGF
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgg094

Both chronic ulcerative colitis and smoking are associated with colorectal cancer in humans. In the present study, we investigated the effects of cigarette smoke (CS) exposure on inflammation-associated tumorigenesis in the mouse colon. Male balb/c mice were allocated into six groups: control, CS (2%), CS (4%), colitis, colitis + CS (2%) and colitis + CS (4%). They were given water or 3% dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis, with or without 1 h daily exposure to 2 or 4% CS. They were then allowed to drink water for 14 days. The cycle of 7 day DSS ± CS/14 day H2O treatments were repeated twice. Mice were killed immediately or 1 month after the three cycles of treatments. Results indicated colonic adenoma was only found in the colitis group (one out of 11), Colitis + CS (2%) group (seven out of 12) and colitis + CS (4%) group (four out of five) 1 month after three cycles of DSS and/or CS treatment. CS exposure dose-dependently increased adenoma formation in mice with inflamed mucosa. CS exposure plus colitis was strongly associated with a high incidence of dysplasia (P < 0.01) and adenocarcinoma formation (P < 0.01) compared with induction of colitis alone. Colitis induced cell proliferation and apoptosis in colonic tissues. Cigarette smoking significantly attenuated the apoptotic effect by DSS probably via the induction of anti-apoptotic protein bcl-2. The ratio of apoptosis over proliferation was also significantly lower in the colitis + CS groups. Vascular endothelial growth factor and angiogenesis in the colon were also increased by cigarette smoking in animals with colitis. In conclusion, CS promotes inflammation-associated adenoma/adenocarcinoma formation in the mouse colon in a dose-dependent manner. This tumor development is associated with the inhibition of cellular apoptosis and supported by increased angiogenesis.