Metabolism and macromolecular binding of benzo(a)pyrene and its noncarcinogenic isomer benzo(e)pyrene in cell culture

Conference · Sun Jan 01 04:00:00 EST 1978

OSTI ID:6539819

Selkirk, J. K.; MacLeod, M. C.

The carcinogenicity of the polycyclic aromatic hydrocarbon benzo(a)pyrene (B(a)P) is thought to result from the metabolic formation of a highly reactive intermediate, 7,8-dihydrodiol-9,10-oxy-B(a)P which subsequently interacts with cellular macromolecules to produce neoplasia. Evidence has been presented implicating similar bay-region diol-epoxides as the ultimate carcinogenic forms of benz(a)anthracene, 7-methyl-benz(a)anthracene, dibenz(a,h)anthracene, and chrysene. Benzo(e)pyrene (B(e)P), on the other hand, is relatively inert when tested for carcinogenicity on mouse skin and rat trachea and when tested for mutagenicity in a mammalian system. This B(e)P molecule contains two (equivalent) bay regions and quantum mechanical model calculations suggest that 9,10-dihydrodiol-11,12-oxy-B(e)P can easily form a reactive bay-region-adjacent carbonium ion. In order to explain the noncarcinogenicity of B(e)P in the context of the bay region theory, we have studied the metabolism of B(e)P by rat liver microsomes and by cultured hamster embryo fibroblasts. In both systems, the major metabolic pathways involve the K-region of B(e)P, with little or no attack on the isolated benzo ring. These results suggest that the lack of carcinogenicity of B(e)P may reflect its preferred mode of interaction with the cellular metabolic machinery.

• Research Organization: Oak Ridge National Lab., TN (USA)
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6539819
• Report Number(s): CONF-781039-4
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
550300 -- Cytology
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
BINDING ENERGY
BODY
CARCINOGENESIS
CELL CONSTITUENTS
CELL CULTURES
COMPARATIVE EVALUATIONS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
EMBRYOS
ENERGY
FIBROBLASTS
GLANDS
HAMSTERS
HYDROCARBONS
ISOMERS
LIVER
MAMMALS
METABOLISM
METABOLITES
MICROSOMES
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PATHOGENESIS
RATS
RODENTS
SOMATIC CELLS
VERTEBRATES