Journal
CANCER RESEARCH
Volume 67, Issue 22, Pages 10766-10773Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-07-1418
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Funding
- NCRR NIH HHS [G12 RR003050, G12-RR03050] Funding Source: Medline
- NIGMS NIH HHS [F31 GM073539, S06-GM08239, S06 GM008239] Funding Source: Medline
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Inflammatory bowel disease (IBD) is a gastrointestinal disorder of unknown etiology or cure. One complication of IBD is an increased risk for development of colon cancer. The aims of this study were to use a previously established rat model of colitis to develop a new model of colitis-associated colon cancer and ascertain the involvement of three cancerrelated genes: K-ras, adenomatous polyposis coli (APC), and p53. Four groups of rats were used: reactivated 1,2-dimethyl-hydrazine [DMH; trinitrobenzene sulfonic acid (TNBS) was used to induce colitis followed by a weekly s.c. dose of DMH], prolonged reactivation (inflammation was induced with TNBS, then maintained twice a week), saline-DMH (animals received saline instead of TNBS followed by a weekly dose of DMH), and normal (received no treatment). Animals were sacrificed at 5, 10, or 15 weeks, and colon samples were taken for pathologic analysis and gene mutation detection. No dysplasia was found in the normal group. The highest incidences of dysplasia were as follows: prolonged reactivation group at 5 weeks (60%), reactivated DMH group at 10 weeks (83%), and saline-DMH group at 15 weeks (67%). Carcinoma was found in both the prolonged reactivation and saline-DMH groups. No mutations were found in the K-ras oncogene; however 62% of the APC samples (exon 15 at nucleotide 2778) and 76% of p53 (exon 6 at nucleotide 1327) showed substitutions. The prolonged reactivation group may be considered a new model of colitis-associated colon cancer, offering the potential to study cancer prevention strategies for patients with IBD.
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