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

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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.