Increased proliferation of middle to distal colonic cells during colorectal carcinogenesis in experimental murine ulcerative colitis.

Abstract:

:Patients with ulcerative colitis (UC) exhibit an increased risk for the development of cancer of the colon and rectum. This association is widely attributed to colonic inflammation. However, the severity of colonic inflammation necessary for the development of dysplasia and/or cancer remains unknown. In this study, we investigated the pattern of cell proliferation in colorectal carcinogenesis in an experimental murine model of UC. Chronic colitis was induced by administration of four cycles of dextran sulfate sodium (DSS) (each cycle: 5% or 2% DSS for 7 days and then distilled water for 14 days). Mice were sacrificed after every cycle and at 120 days following the completion of the fourth cycle. Colonic cell proliferation was immunohistochemically evaluated using the thymidine analogue bromodeoxyuridine and the labeling index (LI) was determined. The incidence of dysplasia and/or cancer was 28%, 6.7%, and 0% in the 5% DSS, 2% DSS, and normal control groups respectively. All gross lesions were present in the middle to distal colon. Disease activity index and total LI after four cycles of DSS were significantly higher in the 5% DSS group compared to the 2% DSS group. In the 5% DSS group, the LI was significantly higher in the middle colon than in the proximal colon. Simple repeated administration of the non-genotoxic colon carcinogen DSS induced dysplasia and/or cancer. In addition, we have demonstrated the presence of regional differences in proliferation pattern between the middle and the proximal colon during carcinogenesis in experimental murine UC. These findings may provide insight into the development of colorectal cancer in humans with long-standing UC.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Inoue T,Murano M,Kuramoto T,Ishida K,Kawakami K,Abe Y,Morita E,Murano N,Toshina K,Nishikawa T,Maemura K,Shimamoto C,Hirata I,Katsu K,Higuchi K

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1457-62

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

18

pub_type

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