Reference SummaryLiu ES, Carcinogenesis 2003 Aug;24(8):1407-13
Title |
Cigarette smoke exposure increases ulcerative colitis-associated colonic adenoma formation in mice. |
Authors |
Liu ES; Ye YN; Shin VY; Yuen ST; Leung SY; Wong BC; Cho CH |
Journal |
Carcinogenesis |
Volume |
24 |
Issue |
8 |
Year |
2003 |
Pages |
1407-13 |
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. |
Links |
J:84490 – MGI References 12807736 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| BALB/c | Intestine - Large Intestine - Colon adenocarcinoma |
|
Intestine - Large Intestine - Colon |
25 |
|
| BALB/c | Intestine - Large Intestine - Colon adenoma |
|
Intestine - Large Intestine - Colon |
0 |
|
| BALB/c | Intestine - Large Intestine - Colon carcinoma | Intestine - Large Intestine - Colon |
0 |
||
| BALB/c | Intestine - Large Intestine - Colon carcinoma |
|
Intestine - Large Intestine - Colon |
0 |
|
| BALB/c | Intestine - Large Intestine - Colon dysplasia |
|
Intestine - Large Intestine - Colon |
0 - 9.1 |
|
| BALB/c | Intestine - Large Intestine - Colon dysplasia |
|
Intestine - Large Intestine - Colon |
42 - 80 |
|
| BALB/c | Intestine - Large Intestine - Colon polyp - adenomatous |
|
Intestine - Large Intestine - Colon |
9.1 |
|
| BALB/c | Intestine - Large Intestine - Colon polyp - adenomatous |
|
Intestine - Large Intestine - Colon |
58 - 80 |