Pretreatment with mixed-function oxidase inducers increases the sensitivity of the hepatocyte/DNA repair assay

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Environmental and Molecular Mutagenesis; (USA)

DOI:https://doi.org/10.1002/em.2850130402· OSTI ID:6896064

Shaddock, J G; Heflich, R H; McMillan, D C; Hinson, J A; Casciano, D A ^[1]

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1. National Center for Toxicological Research, Jefferson, AK (USA) Univ. of Arkansas for Medical Sciences, Little Rock (USA)

A recent National Toxicology Program evaluation indicates that the rat hepatocyte/DNA repair assay has a high false-negative rate and that it is insensitive to some genotoxic hepatocarcinogens as well as other species and organ-specific carcinogens. In this study, the authors examined whether the sensitivity of the hepatocyte/DNA repair assay might be increased through animal pretreatment with various hepatic mixed-function oxidase inducers, i.e., Aroclor 1254, phenobarbital, and 3,3{prime},4,4{prime}-tetrachloroazobenzene (TCAB). The effects on unscheduled DNA synthesis (UDS), a measured of DNA damage and repair, were studied in cultures exposed to known and/or potential carcinogens that had been evaluated as negative or questionable or that produced conflicting results with hepatocytes isolated from uninduced animals. 4,4{prime}-Oxydianiline, 1-nitropy-rene, and TCAB produced concentration-dependent increases in UDS in hepatocytes from rats pretreated with Aroclor 1254. 4,4{prime}-Oxydianiline and TCAB also induced a dose-dependent increase in DNA repair in hepatocytes from rats pretreated with phenobarbital, whereas 1-nitropyrene was negative. These data indicate that the limited sensitivity to chemical carcinogens displayed by the hepatocyte/DNA repair assay may be increased by using hepatocytes isolated from animals exposed to hepatic mixed-function oxidase inducers.

• OSTI ID: 6896064
• Journal Information: Environmental and Molecular Mutagenesis; (USA), Journal Name: Environmental and Molecular Mutagenesis; (USA) Vol. 13:4; ISSN 0893-6692; ISSN EMMUE
• Country of Publication: United States
• Language: English

Related Subjects

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560300 -- Chemicals Metabolism & Toxicology
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANESTHETICS
ANIMAL CELLS
ANIMALS
ANTICONVULSANTS
AROMATICS
AUTORADIOGRAPHY
AZINES
BARBITURATES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHLORINATED AROMATIC HYDROCARBONS
CONDENSED AROMATICS
DNA
DNA REPAIR
DNA REPLICATION
DRUGS
ENZYME INDUCTION
ENZYMES
GENE REGULATION
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROGEN COMPOUNDS
HYPNOTICS AND SEDATIVES
LIVER CELLS
MAMMALS
MIXED-FUNCTION OXIDASES
MOLECULAR BIOLOGY
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PHENOBARBITAL
PYRENE
PYRIMIDINES
RATS
RECOVERY
REPAIR
RODENTS
SOMATIC CELLS
TRITIUM COMPOUNDS
VERTEBRATES