Rapid induction of colonic adenocarcinoma in mice exposed to benzo[a]pyrene and dextran sulfate sodium
Rapid induction of colonic adenocarcinoma in mice exposed to benzo[a]pyrene and dextran sulfate sodium
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DOI：
10.1016/j.fct.2011.07.057
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发表时间：
2011-11-01
影响因子：
4.3
通讯作者：
Tsukidate, Kazuo
中科院分区：
文献类型：
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作者：
Hakura, Atsushi;Seki, Yuki;Tsukidate, Kazuo
此前，我们曾报道，口服环境诱变剂/致癌物质苯并[a]芘(BP)后，小鼠结肠中的突变频率显著增加；然而，这并未导致肿瘤的发展。造成这种情况的原因目前还没有解决。本研究的目的是探索BP在结肠中诱导的高频率突变与随后的肿瘤发展无关的机制。本研究表明，CD2F(1)小鼠口服BP 125 mg/kg/d，连续5天，可在4周(5/8小鼠)和11周(100%小鼠)时导致小鼠结肠腺癌，但仅在饮用水中4%葡聚糖硫酸钠(DSS)诱导炎症的情况下持续2周。这些数据表明，在这个DSS模型中，BP诱导的突变事件会导致小鼠结肠中的肿瘤，而结肠组织不是BP的靶器官。在这个模型中，DSS在具有诱变风险的组织中诱导的炎症是诱导肿瘤的关键。本研究提供了一种新颖、快速、实用的结肠癌发生模型(BP/DSS模型)。(C)2011爱思唯尔有限公司。保留所有权利。
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). (C) 2011 Elsevier Ltd. All rights reserved.