Genotoxicity occurring at the target organs of carcinogenesis is important for understanding the mechanisms of chemical carcinogenicity and also for setting of threshold estimation. In vivo gene mutations have been evaluated by transgenic animal models in which any organ can be targeted; however, the methodologies that have been applied to assess chromosomal aberrations including micronucleus induction, are organ restricted, (often to bone marrow hematopoietic cells, as a common example). For food and food-related chemicals, the digestive tract is the important target organ as it is the organ of first contact. In the present study, we used 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 1,2-dimethylhydrazine (DMH) as model chemicals of carcinogens primarily targeting the colon. We evaluated the applicability of colon cells and hepatocytes, together with bone marrow cells, in the micronucleus assay. Both model chemicals induced micronuclei in the colon, which is the target organ of these carcinogens, after short- and long-term treatment(s). The results demonstrate the target specificity of micronucleus induction and the assay using organs other than bone marrow will play an important role in understanding the mechanism of carcinogenicity and predicting new carcinogenic agents.

中文翻译：

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结肠致癌物诱导的靶标特异性微核：2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶和1,2-二甲基肼。

在致癌目标器官上发生的基因毒性对于理解化学致癌的机理以及设定阈值估计很重要。体内基因突变已通过转基因动物模型进行了评估，在该模型中可以靶向任何器官。但是，已被用来评估包括微核诱导在内的染色体畸变的方法受到器官的限制（通常是骨髓造血细胞）。对于食品和与食品有关的化学物质，消化道是重要的靶器官，因为它是首次接触的器官。在本研究中，我们使用了2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）和1,2-二甲基肼（DMH）作为主要靶向结肠的致癌物模型化学药品。我们在微核试验中评估了结肠细胞和肝细胞以及骨髓细胞的适用性。在短期和长期治疗后，两种模型化学品均会在结肠中诱导微核，结肠是这些致癌物的目标器官。结果证明了微核诱导的靶特异性，并且使用除骨髓以外的器官进行的测定将在理解致癌性机理和预测新的致癌剂中起重要作用。