title: Long-term feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling in rats.
abstract: The Wnt signaling pathway plays an essential role in carcinogenesis, and the amount of fat intake and composition of dietary fatty acids are crucial factors for colon carcinogenesis. We investigated whether various dietary fats affected the Wnt signaling pathway of colon tumorigenesis in azoxymethane (AOM)-treated rats. Male Sprague-Dawley rats were given intraperitoneal injections of AOM and supplemented with 10% corn, olive, beef, and fish oil for 44 wk. Aberrant crypt foci (ACF) and tumors were examined at 12 and 44 wk. Normal appearing colon mucosal proliferation and apoptosis were evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and percentages of fragmented DNA, respectively. Expressions of beta-catenin, cyclin D(1), Wnt2, Wnt3, and Wnt5a of normal appearing colon mucosa were analyzed by Western blot analysis. Long-term dietary corn oil and beef tallow increased ACF, tumor incidence, and tumor numbers in AOM-treated rats. In contrast, both olive and fish oil inhibited them. Dietary corn oil and beef tallow increased BrdU incorporation and the expression of cytosolic beta-catenin and cyclin D(1) and decreased apoptosis in the colon mucosa. Expressions of Wnt2 and Wnt3 in rats fed with beef tallow and Wnt5a in rats fed with corn oil increased with or without AOM-treatment. BrdU-incorporated cells were often observed at the tops of crypts in rats fed with beef tallow, whereas this was not observed in rats fed with the other diet. Long-term high intake of corn oil and beef tallow enhanced cell proliferation through Wnt signaling and modulated the distribution of proliferating cells, which might contribute to promoting effects in colon tumorigenesis.
authors.affiliation: Department of Intestinal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fujise
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Iwakiri
authors.forename: Takashi
authors.initials: T
authors.lastname: Kakimoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Shiraishi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Sakata
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsunada
authors.forename: Akifumi
authors.initials: A
authors.lastname: Ootani
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003314:Corn Oil / Q000008:administration & dosage; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005223:Fats / Q000008:administration & dosage; D005395:Fish Oils / Q000008:administration & dosage; D008297:Male; D000069463:Olive Oil; D010938:Plant Oils / Q000008:administration & dosage; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D056741:Cyclin D; D016213:Cyclins; D004041:Dietary Fats; D005223:Fats; D005395:Fish Oils; D000069463:Olive Oil; D010938:Plant Oils; D051153:Wnt Proteins; D051176:beta Catenin; D003314:Corn Oil; C013698:tallow; D001397:Azoxymethane