Rapid induction of colonic adenocarcinoma in mice exposed to benzo[a]pyrene and dextran sulfate sodium
Autor: | Akiyoshi Suganuma, Kazuo Tsukidate, Yuki Seki, Jiro Sonoda, Kerns William D, Atsushi Hakura, Toyohiko Aoki, Satoru Hosokawa |
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Rok vydání: | 2011 |
Předmět: |
Adenoma
Male Colon Mutagen Inflammation Pharmacology Adenocarcinoma Toxicology medicine.disease_cause chemistry.chemical_compound Mice Oral administration medicine Benzo(a)pyrene Animals Drug Interactions Mutation frequency Dextran Sulfate Sodium Carcinogen Dextran Sulfate General Medicine digestive system diseases chemistry Immunology Colonic Neoplasms Mutation Pyrene medicine.symptom Food Science |
Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 49(11) |
ISSN: | 1873-6351 |
Popis: | 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). |
Databáze: | OpenAIRE |
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