Measurement of unscheduled DNA synthesis and S-phase synthesis in rodent hepatocytes following in vivo treatment: Testing of 24 compounds

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

DOI:https://doi.org/10.1002/em.2850140305· OSTI ID:6866738

Mirsalis, J C; Tyson, C K; Steinmetz, K L; Loh, E K; Hamilton, C M; Bakke, J P ^[1]; Spalding, J W ^[2]

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1. Cellular and Genetic Toxicology Dept., Menlo Park, CA (USA)
2. National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)

The in vivo-in vitro hepatocyte DNA repair assay has been shown to be useful for studying genotoxic hepatocarcinogens. In addition, measurement of S-phase synthesis (SPS) provides an indirect indicator of hepatocellular proliferation, which may be an important mechanism in rodent carcinogenesis. This assay was used to examine 24 chemicals for their ability to induce unscheduled DNA synthesis (UDS) or SPS in Fischer-344 rats or B6C3F1 mice following in vivo treatment. Hepatocytes were isolated by liver perfusion and incubated with {sup 3}H-thymidine following in vivo treatment by gavage. Chemicals chosen for testing were from the National Toxicology Program (NTP) genetic toxicology testing program and most were also evaluated in long-term animal studies conducted by the NTP. Dinitrotoluene and Michler's Ketone induced positive UDS response in rat, while N-nitrosodiethanolamine and selenium sulfide induced equivocal UDS results in mouse and rat, respectively. BCMEE, bromoform, chloroform, PBB, 1,1,2-trichloroethane, and trichloroethylene were all potent inducers of SPS in mouse liver, while C.I. Solvent Yellow 14, and 1,1,2,2-tetrachloroethane yielded equivocal SPS results in rat and mouse, respectively. These results indicate that most of the test compounds do not induced UDS in the liver; however, the significant S-phase response induced by many of these compounds, especially the halogenated solvents, may be an important mechanism in their hepatocarinogenicity.

• OSTI ID: 6866738
• Journal Information: Environmental and Molecular Mutagenesis; (USA), Journal Name: Environmental and Molecular Mutagenesis; (USA) Vol. 14:3; ISSN 0893-6692; ISSN EMMUE
• Country of Publication: United States
• Language: English

Related Subjects

550301 -- Cytology-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATED AROMATICS
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTORADIOGRAPHY
AZINES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BROMINATED ALIPHATIC HYDROCARBONS
BROMOFORM
CARCINOGENESIS
CARCINOGENS
CELL CYCLE
CHALCOGENIDES
CHLORINATED ALIPHATIC HYDROCARBONS
CHLOROFORM
DNA REPAIR
DNA REPLICATION
DYES
HALOGENATED ALIPHATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROGEN COMPOUNDS
LIVER CELLS
MAMMALS
MICE
MOLECULAR BIOLOGY
NITRO COMPOUNDS
NITROSAMINES
NITROSO COMPOUNDS
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC BROMINE COMPOUNDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PYRIMIDINES
RATS
RECOVERY
REPAIR
RIBOSIDES
RODENTS
SELENIUM COMPOUNDS
SELENIUM SULFIDES
SOMATIC CELLS
SULFIDES
SULFUR COMPOUNDS
THYMIDINE
TOLUENE
TRITIUM COMPOUNDS
VERTEBRATES