Aroclor 1254 pretreatment effects on DNA repair in rat hepatocytes elicited by in vivo or in vitro exposure to various chemicals

Environmental Mutagenesis
D Kornbrust, D Dietz


Inducers of liver mixed function oxidase (MFO) activities have profound effects on the genotoxicity of substances that undergo metabolic activation by the MFO system. The polychlorinated biphenyl mixture Aroclor 1254 is a broad-spectrum inducer of liver MFO activities that has been employed as a pretreatment to augment the metabolic activation capabilities of rat liver fractions used in a number of short-term tests for genotoxicity, including the Ames Salmonella/bacterial mutagenicity assay. The present study was designed to characterize the effects of Aroclor pretreatment of rats on the DNA repair responses elicited by various chemicals in the in vitro hepatocyte primary culture/DNA repair (HPC/DR) assay as well as the in vivo/in vitro HPC/DR assay. The amount of DNA repair produced in vitro by diethylnitrosamine (DEN), benzo(a)pyrene (B(a)P), 3-methylcholanthrene (3-MC), 2-acetylaminofluorene (2-AAF), o-aminoazotoluene (o-AT), and aflatoxin B1 (AFB1) was significantly greater in hepatocytes derived from Aroclor-pretreated rats than in control rat hepatocytes; in vitro responses to dimethylnitrosamine (DMN), 7,12-dimethylbenzanthracene (DMBA), benzidine (BZ), and 2-naphthylamine (2-NA) were not significantly affected by Aroclo...Continue Reading


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