title: Cigarette smoke exposure increases ulcerative colitis-associated colonic adenoma formation in mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Edgar S L
authors.initials: ES
authors.lastname: Liu
authors.forename: Yi-Ni
authors.initials: YN
authors.lastname: Ye
authors.forename: Vivian Y
authors.initials: VY
authors.lastname: Shin
authors.forename: Siu-Tsan
authors.initials: ST
authors.lastname: Yuen
authors.forename: Suet-Yi
authors.initials: SY
authors.lastname: Leung
authors.forename: Benjamin C Y
authors.initials: BC
authors.lastname: Wong
authors.forename: Chi-Hin
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000236:Adenoma / Q000209:etiology* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000209:etiology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D016228:Endothelial Growth Factors / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000209:etiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016264:Dextran Sulfate