Induction of chromosome aberrations and sister chromatid exchange by indirectly acting mutagens in immortal mouse and rat hepatocyte lines

Abstract

Two immortalized, differentiated mouse (FMH-202) and rat (NRL-Cl-A) hepatocyte lines were examined for their capacity to activate the indirectly acting mutagens aflatoxin B1 (AFB1), cyclophosphamide (CP), benzo[a]pyrene (BaP) and 7,12-dimethylbenz[a]anthracene (DMBA) into DNA reactive metabolites as determined by the induction of structural chromosome aberrations (CA) and sister chromatid exchange (SCE). The rat and mouse hepatocyte lines were able to efficiently activate either AFB1, BaP and DMBA, or BaP and DMBA, respectively, as shown by significant clastogenic responses. SCE induction was apparent in both cell lines in response to each of the compounds. Due to the observed long-term maintenance of various liver specific functions (at least 3-4 years) as well as the capability to metabolize xenobiotics (at least 30 passages) these cells may be a suitable assay system for the detection of indirectly acting mutagens.