Comparative investigation of antimutagenic activity of sterically hindered phenols
Mutagenic properties of primarily inactive carcinogenic polycyclic aromatic hydrocarbons (PAH) are manifested after metabolic oxidation by microsomal enzymes. It has been established that activation of carcinogens in biological systems is accompanied by intensification of free-radical processes, effective inhibition of which is achieved by sterically hindered phenols (SHP). The authors studied the effect of SHP on the mutagenic activity of benzo(a)pyrene (BP) using estimation of induced direct gene mutation at the locus for hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) in somatic Chinese hamster cells of line V-79 cultured in vitro and with estimation of the induction of micronuclei in polychromatophilic erythrocytes of mouse bone marrow in vivo. The reference mutagen was BP from Fluka and the following SHP were used: dibunol, F-800, and F-804. Genetic activity of each substance tested and their combination was studied in an in vitro system under conditions of metabolic activation by mouse liver microsomes and in vivo according to induction of micronuclei in polychromatophilic bone marrow erythrocytes in (CBA x C57B1/6J)F/sub 1/ mice 60-80 days old, which reflects gross defects of chromosomes at the erythroblast stage. In order to establish optimal time for recording the frequency of induction of micronuclei, bone marrow samples were taken from the animals, 24, 48, 72, and 96 h after a single intraperitoneal injection of the agents. The BP was dissolved in sunflower oil and used in a concentration constituting 1/3 of the lowest lethal dose in mice. The SHP was then dissolved in water or dimethyl sulfoxide and administered in a ratio with BP of 1:1 or 1:0.5. The smears were then stained in methanol, washed with twice-distilled water, and stained in 7% Giemsa solution.
- Research Organization:
- N. I. Vavilov Institute of General Genetics, Moscow, USSR
- OSTI ID:
- 5844316
- Journal Information:
- Dokl. Biol. Sci. (Engl. Transl.); (United States), Vol. 280:1-6; Other Information: Translated from Dokl. Akad. Nauk SSSR; 280: No. 6, 1441-1444(Feb 1985)
- Country of Publication:
- United States
- Language:
- English
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ANTIOXIDANTS
BIOLOGICAL EFFECTS
BENZOPYRENE
METABOLIC ACTIVATION
MUTAGENESIS
BONE MARROW CELLS
GENE MUTATIONS
CHO CELLS
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
ENZYME ACTIVITY
PHENOLS
POLYCYCLIC AROMATIC HYDROCARBONS
CARCINOGENESIS
CHROMOSOMAL ABERRATIONS
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
ERYTHROCYTES
GENES
MATERIALS TESTING
MICE
ANIMAL CELLS
ANIMALS
AROMATICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
ENZYMES
GLYCOSYL TRANSFERASES
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
MATERIALS
MUTATIONS
ORGANIC COMPOUNDS
PATHOGENESIS
PENTOSYL TRANSFERASES
RODENTS
SOMATIC CELLS
TESTING
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology