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

为了建立一种高灵敏度的检测化学致突变性和致瘤性的方法，我们用Ogg 1、Mutyh和Msh 2缺陷小鼠进行了KBrO_3致突变和致瘤实验。与野生型和杂合子小鼠相比，我们观察到Mutyh或Msh 2缺陷小鼠小肠中肿瘤形成增强。这些结果表明，Mutyh-或Msh 2-缺陷小鼠是理想的动物模型，用于检查感兴趣的化学品的致瘤性。Ogg 1基因缺陷小鼠的肿瘤数量略有增加，但KBrO_3诱发的突变增加的程度与Mutyh基因缺陷小鼠几乎相同，这表明诱导细胞死亡可能比抑制突变在避免氧化应激引起的肠道肿瘤发生中起更重要的作用。

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.