Metabolism of acrylonitrile and interactions

Thesis/Dissertation · Wed Jan 01 04:00:00 EST 1986

OSTI ID:7065453

Hogy, L L

Metabolic activation by liver microsomes is necessary for the covalent binding to DNA of acrylonitrile, a widely used industrial chemical. However, tumor formation is localized in the brain, not in the liver. The reasons for such target organ specificity and the mechanism of carcinogenicity are unknown, and studies were performed to provide insights into these events. The metabolism of acrylonitrile was studied in isolated rat hepatocytes to establish the quantitative relationship between oxidative and conjugative metabolism. Approximately 85% of the acrylonitrile reacted with glutathione to form S-(2-cyanoethyl)glutathione while another 5% alkylated protein, especially by cyanoethylation of sulfhydryl groups. About 10% of the acrylonitrile was metabolized to the relatively stable epoxide, 2-cyanoethylene oxide. Further experiments were carried out to study in vivo any genetic damage by acrylonitrile and assess the role of 2-cyanoethylene oxide. Unscheduled DNA synthesis was observed in the livers, but not the brains of acrylonitrile-treated rats. When perfused rat livers were treated with acrylonitrile, 2-cyanoethylene oxide accumulated in the perfusate. 2-Cyano-(2,3-/sup 14/C)-ethylene oxide administered to rats intraperitoneally was found to label both liver and brain protein, but no covalent binding to nucleic acids was detected. These results demonstrate that acrylonitrile has some limited potential for genotoxicity in vivo and that the epoxide can circulate from the liver to the brain to alkylate macromolecules in a carcinogenic target organ generally less capable of DNA repair.

• Research Organization: Vanderbilt Univ., Nashville, TN (USA)
• OSTI ID: 7065453
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACRYLONITRILE
ANIMAL CELLS
ANIMALS
BIOCHEMISTRY
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
BRAIN
CARBON 14 COMPOUNDS
CARCINOGENESIS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
CONFIGURATION INTERACTION
DIGESTIVE SYSTEM
DISEASES
DISTRIBUTION
DNA
DNA REPAIR
GLANDS
IN VIVO
LABELLED COMPOUNDS
LIVER
LIVER CELLS
MAMMALS
METABOLIC ACTIVATION
MICROSOMES
NEOPLASMS
NERVOUS SYSTEM
NITRILES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PATHOGENESIS
RATS
RECOVERY
REPAIR
RODENTS
SOMATIC CELLS
TISSUE DISTRIBUTION
VERTEBRATES