The more an ulcerative colitis is repeated, the more the risk of colorectal carcinogenesis is increased in mice.
The incidence of colorectal carcinogenesis is increased in patients with ulcerative colitis. We investigated the effects of repetitive diarrhea on colorectal carcinogenesis in mice singly pretreated by a low-dose of chemical carcinogen. Mucosal changes were investigated in mice pretreated with a single intraperitoneal injection of 8.0 mg/kg body weight of azoxymethane prior to a repetitive oral administration of 3% dextran sulphate sodium to induce chronic diarrhea. Repetitive treatment with dextran sulphate sodium induced a cycle of chronic diarrhea-remission in the colorectum. Five submucosal-invasive adenocarcinomas and 65 high-grade dysplasias were found in 15 mice that underwent azoxymethane-pretreatment with 3 cycles of 3% dextran sulphate sodium-exposure, i.e. colorectal carcinogenesis was observed mainly in the left side of the large intestine within 11 weeks after the initial treatment with carcinogen. Consequently, thymidine kinase was expressed and activated, and an increase in bromodeoxyuridine-immuno-reactive (S-phase) cells was observed in the regenerating mucosa and the colorectum with tumorous lesions. Colorectal carcinogenesis developed with the increasing duration of diarrhea induced by 3% dextran sulphate sodium in mice pretreated by a single injection of a small dosage of azoxymethane during the comparatively short period of this experimental colitis system.
Mitamura
Tadasu
T
Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Sakamoto
Shinobu
S
Sassa
Shuji
S
Suzuiki
Satoe
S
Kudo
Hideki
H
Okayasu
Isao
I
D000230:Adenocarcinoma / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001397:Azoxymethane; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced / Q000150:complications; D005243:Feces; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D012007:Rectum / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012307:Risk Factors; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000378:metabolism; D013940:Thymidylate Synthase / Q000096:biosynthesis / Q000378:metabolism
D002273:Carcinogens; D016264:Dextran Sulfate; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; D001397:Azoxymethane