Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice
Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice
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DOI：
10.1093/carcin/bgi205
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发表时间：
2006-01-01
期刊：
影响因子：
4.7
通讯作者：
Tanaka, T
中科院分区：
文献类型：
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作者：
Suzuki, R;Kohno, H;Tanaka, T
我们最近建立了一种结肠炎相关结肠癌的小鼠模型，用偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)联合治疗雄性ICR小鼠。然而，不同菌株对AOM/DSS诱导的小鼠结肠癌的敏感性的差异尚不清楚。这项研究的目的是确定四个近交系小鼠对我们的结肠癌发生模型的敏感性是否存在遗传决定的差异。雄性Balb/c、C3H/HEN、C57BL/6N和DBA/2N小鼠一次性腹腔注射AOM(10 mg/kg体重)，然后在饮用水中加入1%DSS(w/v)，连续4天，然后不再接受进一步治疗，直到16周。在研究结束时(第18周)，所有小鼠都被处死，并对它们的结肠进行组织病理学分析。结肠腺癌的发病率为100%，且呈多发性(No.Balb/c小鼠为7.7+/-4.3，C57BL/6N小鼠为50%，复数为1.0+/-1.2。另一方面，C3H/HEN小鼠和DBA/2N小鼠仅发生少量结肠腺瘤，但未发生腺癌(发生率29%，复数为0.7+/-1.5)和DBA/2N小鼠(发生率20%，复数0.2+/-0.4)。AOM和DSS组小鼠炎症反应和免疫组织化学阳性积分由高到低依次为：C3H/HEN>；Balb/c>；DBA/2N>；C57BL/6N和Balb/c>；C57BL/6N>；C3H/HEN>；DBA/2N。因此，我们的结果表明，在AOM/DSS诱导的结肠肿瘤发生的易感性上存在菌株差异。这些差异可能直接受到亚硝化应激反应的影响，亚硝化应激是由于DSS引起的炎症。
We have recently developed a mouse model for colitis-related colon carcinogenesis by a combined treatment with azoxymethane (AOM) and dextran sodium sulfate (DSS) in male ICR mice. However, strain differences in the sensitivity to AOM/DSS-induced colon carcinogenesis in mice have yet to be elucidated. The aim of this study was to determine the presence of any genetically determined differences in sensitivity to our model of colon carcinogenesis in four inbred strains of mice. Male Balb/c, C3H/HeN, C57BL/6N and DBA/2N mice were given a single intraperitoneal injection of AOM (10 mg/kg body wt), followed by 1% DSS (w/v) in drinking water for 4 days, and thereafter they received no further treatment for up to 16 weeks. At the end of the study (Week 18), all mice were killed and a histopathological analysis of their colon was performed. The incidence of colonic adenocarcinoma was 100% with a multiplicity (no. of tumors/mouse) of 7.7 +/- 4.3 in the Balb/c mice and 50% with a multiplicity of 1.0 +/- 1.2 in the C57BL/6N mice. On the other hand, only a few colonic adenomas, but no adenocarcinomas, developed in the C3H/HeN mice (29% incidence with a multiplicity of 0.7 +/- 1.5) and the DBA/2N mice (20% incidence with a multiplicity of 0.2 +/- 0.4). The inflammation and immunohistochemical nitrotyrosine-positivity scores of the mice treated with AOM and DSS in the decreasing order were as follows: C3H/HeN > Balb/c > DBA/2N > C57BL/6N and Balb/c > C57BL/6N > C3H/HeN > DBA/2N, respectively. Our results thus indicated the presence of strain differences in the susceptibility to AOM/DSS-induced colonic tumorigenesis. These differences may have been directly influenced by the response to nitrosation stress due to the inflammation caused by DSS.