title: 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.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Osaka 569-8686, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Murano
authors.forename: Takanori
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Kumi
authors.initials: K
authors.lastname: Ishida
authors.forename: Ken
authors.initials: K
authors.lastname: Kawakami
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Abe
authors.forename: Eijiro
authors.initials: E
authors.lastname: Morita
authors.forename: Naoko
authors.initials: N
authors.lastname: Murano
authors.forename: Ken
authors.initials: K
authors.lastname: Toshina
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Maemura
authors.forename: Chikao
authors.initials: C
authors.lastname: Shimamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Katsu
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D002273:Carcinogens; D003093:Colitis, Ulcerative / Q000150:complications*; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000473:pathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D002273:Carcinogens; D016264:Dextran Sulfate