Chimeric mice with human hepatocytes: A new system for genotoxicity studies

Abstract Genotoxicity assaysare characterized by a method, an in vitro or in vivo target, and an endpoint. Many cell types have been used as targets, including bacterial cells, cultured mammalian cells, and rodent cells in vivo . Human cells are the most important target for evaluating the risk to humans associated with exposure to chemicals. Almost exclusively, the human cells used in genotoxicitytests have been cultured cells. Here, we have tested human hepatocytes in PXB-mice ® , chimeric mice in which the liver has been repopulatedwith human hepatocytes, as a source of target cells for in vivo genotoxicity assays. We applied the single-cell gel electrophoresis ( comet) assayto detect DNA damage and the micronucleus assayto evaluate chromosomal aberrations. These chimeric mice can serve as a valuable model system for genotoxicity assays.