Comparison of rat and hamster hepatocyte primary culture/DNA repair assays
Previous studies have demonstrated marked differences in the capacity of hepatocytes from rats or hamsters to mediate the metabolic activation of chemical carcinogens to genotoxic (i.e., mutagenic) products. Thus far, very few investigations of species differences in DNA repair have been performed. Therefore, a comparison of the relative extent of DNA repair elicited by various genotoxic chemicals in rat and hamster hepatocyes was conducted, using the hepatocyte primary culture/DNA repair (HPC/DR) assay. Of the ll chemicals tested, eight were more potent in inducing DNA repair in hamster hepatocytes than in rat hepatocytes. Dimethylnitrosamine, diethylnitrosamine, 2-acetylaminofluorene, 9-aminoacridine, pararosaniline hydrochloride, 1-naphthylamine, benzidine and 1,2,3,4-diepoxybutane were all active in hamster hepatocytes at a concentration at least ten times less than the lowest effective concentration in rat hepatocytes. The direct-acting alkylating agent, methylmethane sulfonate, was equipotent inducing DNA repair in both rat and hamster hepatocytes, indicating that the differences in DNA repair observed for the other chemicals were probably not a result of species differences in DNA repair capacities. In contrast, 1-nitropyrene produced a greater DNA repair response in rat hepatocyes than hamster hepatocytes, while the bacterial mutagen 3-(chloromethyl)pyridine hydrochloride was inactive in both hepatocyte systems. These studies demonstrate the feasibility of using hamster hepatocytes in the HPC/DR assay and illustrate the utility of performing the assay with hepatocytes from more than one species.
- Research Organization:
- Research Triangle Inst., Research Triangle Park, NC
- OSTI ID:
- 6595567
- Journal Information:
- Environ. Mutagen.; (United States), Vol. 6:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ACRIDINES
METABOLIC ACTIVATION
ANILINE
BENZIDINE
DNA REPAIR
GENETIC VARIABILITY
FLUORINE COMPOUNDS
NITROSAMINES
ANIMAL CELLS
CARCINOGENS
COMPARATIVE EVALUATIONS
HAMSTERS
LIVER
MUTAGENS
RATS
AMINES
ANIMALS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BIOLOGICAL VARIABILITY
BODY
DIGESTIVE SYSTEM
GLANDS
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
MAMMALS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIDINES
RECOVERY
REPAIR
RODENTS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)