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

Journal Article · Mon Dec 31 23:00:00 EST 1984 · Environ. Mutagen.; (United States)

DOI:https://doi.org/10.1002/em.2860070607· OSTI ID:6178381

Kornbrust, D; Dietz, D

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)P0, 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. The pretreatment-related potentiation of DNA repair observed for 6 out of 12 compounds tested in vitro was considered to be due to enhanced metabolic activation. These results suggested that pretreatment with Aroclor may increase the sensitivity of the in vitro HPC/DR assay to certain compounds. In contrast, Aroclor pretreatment had little effect on the amount of hepatocellular DNA repair elicited by in vivo administration of DMN, DEN, o-AT, 2-AFF, 3-MC, or AFB1, which indicated that this pretreatment regimen may have little utility for improving the sensitivity of the in vivo/in vitro HPC/DR assay.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC
• OSTI ID: 6178381
• Journal Information: Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 7:6; ISSN ENMUD
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFLATOXIN
AMINES
ANIMAL CELLS
ANIMALS
ANTIGENS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHLORINATED AROMATIC HYDROCARBONS
CONDENSED AROMATICS
DIMETHYLBENZANTHRACENE
DNA REPAIR
ELEMENTS
ENZYMES
ESTERS
FLUORINE
HALOGENATED AROMATIC HYDROCARBONS
HALOGENS
HYDROCARBONS
IN VITRO
IN VIVO
LIVER CELLS
MAMMALS
MATERIALS
METABOLIC ACTIVATION
METHYL METHANESULFONATE
MIXED-FUNCTION OXIDASES
MUTAGEN SCREENING
MUTAGENS
NITROSAMINES
NITROSO COMPOUNDS
NONMETALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
RATS
RECOVERY
REPAIR
RODENTS
SCREENING
SOMATIC CELLS
SULFONIC ACID ESTERS
TOXIC MATERIALS
TOXINS
VERTEBRATES