Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures

Journal Article · Tue Jan 01 04:00:00 EST 1985 · J. Toxicol. Environ. Health; (United States)

DOI:https://doi.org/10.1080/15287398509530651· OSTI ID:5434204

Mendoza-Figueroa, T; Lopez-Revilla, R; Villa-Trevino, S

The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with (/sup 3/H) dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: 1) the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and 2) the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340..mu..M) and to the precarcinogens benzo(a)pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

• Research Organization: Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico D.F., Mexico
• OSTI ID: 5434204
• Journal Information: J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 15:2; ISSN JTEHD
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AZINES
BENZOPYRENE
BODY
CARBONIC ACID DERIVATIVES
CARCINOGENESIS
CELL CULTURES
CHLORINATED AROMATIC HYDROCARBONS
CONDENSED AROMATICS
DATA
DIGESTIVE SYSTEM
DNA
EXPERIMENTAL DATA
GLANDS
GUANIDINES
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
INFORMATION
LABELLED COMPOUNDS
LIVER
LIVER CELLS
MAMMALS
METABOLIC ACTIVATION
MOLECULAR WEIGHT
NITROSAMINES
NITROSO COMPOUNDS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
NUMERICAL DATA
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PYRIMIDINES
RATS
RIBOSIDES
RODENTS
SOMATIC CELLS
STRAND BREAKS
SYNERGISM
THYMIDINE
TOXICITY
TRITIUM COMPOUNDS
VERTEBRATES