title: Rapid induction of colonic adenocarcinoma in mice exposed to benzo[a]pyrene and dextran sulfate sodium.
abstract: Previously, we reported that the mutation frequency was markedly increased in the colon after the oral treatment of mice with an environmental mutagen/carcinogen, benzo[a]pyrene (BP); however this was not followed by tumor development. The reasons for this are as yet unresolved. The purpose of the present study is to explore the mechanisms why a high frequency of mutations induced by BP in the colon is not associated with subsequent tumor development. We show in this study that oral administration of BP to CD2F(1) mice at 125 mg/kg/day for 5 days can lead to adenocarcinomas in the mouse colon both at Weeks 4 (5/8 mice) and 11 (100% of mice), but only in the presence of inflammation induced by 4% dextran sulfate sodium (DSS) in the drinking water for up to 2 weeks. These data indicate that, in this DSS model, BP induced mutagenic events lead to tumors in the mouse colon, a tissue which is not a BP target organ. DSS-induced inflammation in a tissue primed with mutagenic risk is a key to the induction of tumors in this model. This study provides a novel, rapid and useful colon carcinogenesis model (BP/DSS model).
authors.affiliation: Global Drug Safety, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. a-hakura@hhc.eisai.co.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hakura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Seki
authors.forename: Jiro
authors.initials: J
authors.lastname: Sonoda
authors.forename: Satoru
authors.initials: S
authors.lastname: Hosokawa
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Aoki
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Suganuma
authors.forename: William D
authors.initials: WD
authors.lastname: Kerns
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsukidate
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D004347:Drug Interactions; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D051379:Mice; D009154:Mutation
chemical_list: D001564:Benzo(a)pyrene; D016264:Dextran Sulfate