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This work describes the primary rodent hepatocyte micronucleus (MN) assay starting from its beginnings as an ex vivo/in vitro assay to the final development of culture conditions enabling the in vitro proliferation of primary hepatocytes. It addresses the sensitivity of this cellular system and the particular features of hepatocytes that lead to higher frequencies of micronucleated cells such as polyploidy and the related formation of multipolar mitosis. Last, it gives information on the potential applications apart from the mere testing of suspect chemicals. These applications include the evaluation of the genotoxic potential of complex environmental mixtures, biomonitoring and antimutagenicity testing.

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