Induction of colon tumors in C57BL/6J mice fed MeIQx, IQ, or PhIP followed by dextran sulfate sodium treatment
Induction of colon tumors in C57BL/6J mice fed MeIQx, IQ, or PhIP followed by dextran sulfate sodium treatment
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DOI：
10.1093/toxsci/kfi079
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Hirose, M
中科院分区：
文献类型：
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作者：
Nishikawa, A;Imazawa, T;Hirose, M
杂环胺（HCAs）在啮齿类动物的多个器官中均可诱导肿瘤，但除MeIQ和PhIP外，其他HCAs如MeIQx和IQ在小鼠中均不能诱导结肠肿瘤，而MeIQ、IQ和PhIP在大鼠中具有结肠致瘤性。最近，我们发现饮食中的MeIQx在亚致癌剂量（如300 ppm）下对两种不同类型的报告基因转基因小鼠的结肠和肝脏产生遗传毒性。然而，在本研究中，即使在300 ppm的浓度下喂养78周，饮食中MeIQx也没有显著诱导C57BL/6J小鼠或gpt delta小鼠的任何肿瘤，这表明单独使用MeIQx治疗不足以促进结肠肿瘤。为了阐明HCAs诱导结肠肿瘤的可能性，C57BL/6J小鼠分别以300 ppm的剂量给药MeIQx、IQ或PhIP 12周，之后两次用葡聚糖硫酸钠（DSS）治疗，每次1周，间隔2周。20周后，MeIQx组、IQ组和PhIP组结肠肿瘤包括腺癌的发生率分别为22%、24%和45%，与单独使用DSS组（0%）相比差异有统计学意义（p < 0.05或0.01）。因此，我们的结果清楚地表明，在促进结肠肿瘤的实验条件下，除PhIP外，MeIQx和IQ也能诱导小鼠结肠肿瘤。
Heterocyclic amines (HCAs) have been shown to induce tumors in several organs of rodents, but except for MeIQ and PhIP, other HCAs such as MeIQx and IQ consistently failed to induce colon tumors in mice, whereas MeIQ, IQ, and PhIP exerted colon tumorigenicity in rats. Recently, we found that dietary MeIQx induces genotoxicity in the colon as well as the liver of two different types of reporter gene transgenic mice at subcarcinogenic doses such as 300 ppm. However, in the present study, dietary MeIQx did not significantly induce any tumors in C57BL/6J mice or gpt delta mice even when fed at 300 ppm for 78 weeks, suggesting that the treatment of MeIQx alone was not sufficient to promote colon tumors. In order to clarify a possibility whether such HCAs can induce colon tumors, C57BL/6J mice were fed MeIQx, IQ, or PhIP at a dose of 300 ppm for 12 weeks and, thereafter, twice received 1-week treatment with dextran sulfate sodium (DSS), 2 weeks apart. After 20 weeks, colon tumors including adenocarcinomas were found at incidences of 22%, 24%, and 45% in the groups receiving MeIQx, IQ, and PhIP, respectively, which were significantly (p < 0.05 or 0.01) different from the DSS alone value (0%). Thus our results clearly indicate that, in addition to PhIP, MeIQx and IQ can induce colon tumors in mice under an experimental condition promoting colon tumors.