title: Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice.
abstract: Histamine and histamine receptors (Hrhs) have been identified as critical molecules during inflammation and carcinogenesis. This study was conducted to determine the effects of Hrh1-Hrh3 antagonists on inflammation-associated colorectal carcinogenesis. Male ICR mice were treated with azoxymethane (AOM, 10 mg/kg bw, i.p.) and 1.5% dextran sodium sulfate (DSS, drinking water for 7 days) to induce colorectal carcinogenesis. The mice were then fed diets containing test chemical (500 ppm terfenadine, 500 ppm cimetidine or 10 ppm clobenpropit) for 15 weeks. At week 18, feeding with the diets containing cimetidine (Hrh2 antagonist) and clobenpropit (Hrh3 antagonist/inverse agonist) significantly lowered the multiplicity of colonic adenocarcinoma. Terfenadine (Hrh1 antagonist) did not affect AOM-DSS-induced colorectal carcinogenesis. Adenocarcinoma cells immunohistochemically expressed Hrh1, Hrh2, Hrh3 and Hrh4 with varied intensities. Because clobenpropit is also known to be a Hrh4 receptor agonist, Hrh2, Hrh3 and Hrh4 may be involved in inflammation-related colorectal carcinogenesis. Additional data, including the mRNA expression of pro-inflammatory cytokines and inducible inflammatory enzymes in the colonic mucosa, are also presented.
authors.affiliation: Department of Diagnostic Pathology (DDP) and Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu City, Gifu 500-8513, Japan. takutt@gmhosp.gifu.gifu.jp.|Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. takutt@gmhosp.gifu.gifu.jp.
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. kottii924@yahoo.co.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kochi
authors.affiliation: Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. shirakamiyy@yahoo.co.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.affiliation: Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki 503-8502, Japan. ta_mori04@yahoo.co.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Diagnostic Pathology (DDP) and Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu City, Gifu 500-8513, Japan. mulmirry@yahoo.co.jp.|Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. mulmirry@yahoo.co.jp.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kurata
authors.affiliation: Department of Diagnostic Pathology (DDP) and Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu City, Gifu 500-8513, Japan. naoki@watanabe.name.
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. hmori@gifu-u.ac.jp.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. shimim-gif@umin.ac.jp.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
keywords: antagonists; azoxymethane; chemoprevention; colorectal cancer; dextran sodium sulfate; histamine receptors; inflammatory bowel disease