Cigarette smoke exposure increases ulcerative colitis-associated colonic adenoma formation in mice.
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.
Liu
Edgar S L
ES
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
Ye
Yi-Ni
YN
Shin
Vivian Y
VY
Yuen
Siu-Tsan
ST
Leung
Suet-Yi
SY
Wong
Benjamin C Y
BC
Cho
Chi-Hin
CH
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
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