Inhibition of DNA synthesis by chemical carcinogens in cultures of initiated and normal proliferating rat hepatocytes
Rat hepatocytes in primary culture can be stimulated to replicate under the influence of rat serum and sparse plating conditions. Higher replication rates are induced by serum from two-thirds partially hepatectomized rats. The effects of carcinogens and noncarcinogens on the ability of hepatocytes to synthesize DNA were examined by measuring the incorporation of (3H)thymidine by liquid scintillation counting and autoradiography. Hepatocyte DNA synthesis was not decreased by ethanol or dimethyl sulfoxide at concentrations less than 0.5%. No effect was observed when 0.1 mM ketamine, Nembutal, hypoxanthine, sucrose, ascorbic acid, or benzo(e)pyrene was added to cultures of replicating hepatocytes. Estrogen, testosterone, tryptophan, and vitamin E inhibited DNA synthesis by approximately 50% at 0.1 mM, a concentration at which toxicity was noticeable. Several carcinogens requiring metabolic activation as well as the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine interfered with DNA synthesis. Aflatoxin B1 inhibited DNA synthesis by 50% (ID50) at concentrations between 1 X 10(-8) and 1 X 10(-7) M. The ID50 for 2-acetylaminofluorene was between 1 X 10(-7) and 1 X 10(-6) M. Benzo(a)pyrene and 3'-methyl-4-dimethylaminoazobenzene inhibited DNA synthesis 50% between 1 X 10(-5) and 1 X 10(-4) M. Diethylnitrosamine and dimethylnitrosamine (ID50 between 1 X 10(-4) and 5 X 10(-4) M) and 1- and 2-naphthylamine (ID50 between 1 X 10(-5) and 5 X 10(-4) M) caused inhibition of DNA synthesis at concentrations which overlapped with concentrations that caused measurable toxicity.
- Research Organization:
- Duke Univ. Medical Center, Durham, NC
- OSTI ID:
- 5776846
- Journal Information:
- Cancer Res.; (United States), Vol. 45:1
- Country of Publication:
- United States
- Language:
- English
Similar Records
Inhibition of cellular DNA synthesis in serum stimulated populations of TC-7 monkey kidney cells by benzo(a)pyrene-7,8-dihydrodiol-9-10-oxide
Inhibition of DNA synthesis, independent of DNA adduct formation, by benzo(a)pyrene diol epoxide in mammalian cells
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AFLATOXIN
TOXICITY
AMINES
ASCORBIC ACID
AZO COMPOUNDS
BENZENE
BENZOPYRENE
DMSO
ESTROGENS
ETHANOL
FLUORENE
HYPOXANTHINE
LIVER CELLS
DNA REPLICATION
NITROSO COMPOUNDS
SACCHAROSE
TESTOSTERONE
VITAMINS
AUTORADIOGRAPHY
CARCINOGEN SCREENING
CARCINOGENS
CELL CULTURES
CELL KILLING
DOSE-RESPONSE RELATIONSHIPS
METABOLIC ACTIVATION
RATS
RESPONSE MODIFYING FACTORS
SCINTILLATION COUNTING
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALCOHOLS
ANDROGENS
ANDROSTANES
ANIMAL CELLS
ANIMALS
ANTIGENS
AROMATICS
AZAARENES
AZINES
CARBOHYDRATES
CONDENSED AROMATICS
COUNTING TECHNIQUES
DISACCHARIDES
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROCARBONS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
OLIGOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PURINES
PYRIMIDINES
RIBOSIDES
RODENTS
SACCHARIDES
SCREENING
SOMATIC CELLS
STEROID HORMONES
STEROIDS
SULFOXIDES
TOXIC MATERIALS
TOXINS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550201 - Biochemistry- Tracer Techniques