A highly sensitive assay system for examining chemical mutagenesity and carcinogenesity using DNA repair-deficient mice

为了建立一种检测化学诱变性和致瘤性的高灵敏度检测系统，我们使用Ogg1-、Mutyh-或msh2缺陷小鼠进行了kbro_3诱导的诱变和致瘤实验。我们观察到，与野生型和杂合小鼠相比，Mutyh-或msh2缺陷小鼠的小肠中肿瘤形成增强。这些结果表明，Mutyh-或msh2缺陷小鼠是检测相关化学物质致瘤性的理想动物模型。ogg1缺陷小鼠的肿瘤数量略有增加，kbro_3诱导的突变增加程度与mutyh缺陷小鼠几乎相同，这表明在避免氧化应激引起的肠道肿瘤发生方面，诱导细胞死亡可能比抑制突变发挥更重要的作用。

In order to establish a highly sensitive assay system for examining chemical mutagenesity and tumorigenesity, we performed KBrO_3-induced mutagenesis and tumorigenesis experiments using Ogg1-, Mutyh- or Msh2-deficient mice. We observed an enhanced tumor-formation in the small intestines of Mutyh- or Msh2-deficient mice, as compared with wild type and heterozygous mice. These results indicate that Mutyh- or Msh2-deficient mice are ideal animal models for examining tumorigenesity of chemicals of interest. The number of tumors was marginally increased in Ogg1-deficient mice in which the increased KBrO_3-induced mutagenesis was observed at an almost same extent as in Mutyh-deficient mice, suggesting that the induction of cell death might play a more important role than the suppression of mutagenesis for avoiding intestinal tumorigenesis caused by oxidative stress.