Search for in vivo early prediction markers of carcinogenicity based on the induction mechanism of karyomegaly

在致癌的靶细胞中，有一些致癌物可以诱导细胞核增大，反映细胞周期的异常。在这项研究中，我们发现，在治疗28天后，促进细胞增殖的致癌物增加了大鼠致癌靶器官中的细胞凋亡和M期中断细胞，因此，我们获得了早期预测致癌性的候选标记物。我们还发现，在致癌过程的早期，核致癌物的促癌作用可能通过p16、INK4A基因的表观遗传修饰而导致细胞周期调控的中断。

There are carcinogens that can induce karyomegaly reflecting cell cycle aberration in carcinogenic target cells. In this study, we found that carcinogens evoking facilitation of cell proliferation increased apoptosis and M phase-disrupting cells in the carcinogenic target organs after28-day treatment in rats, and thus, we obtained candidates for early prediction markers ofcarcinogenicity. We also found that tumor promotion with karyomegaly-inducing hepatocarcinogens may cause disruption of cell cycle regulation through epigenetic gene modification of p16^Ink4a in the carcinogenic process from the early stage.