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Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polynculear aromatic hydrocarbons

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
 [1]; ; ; ; ;
  1. National Cancer Inst., Bethesda, MD
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Cultured human bronchial explants activated benzo(a)pyrene (BzaP) into electrophilic metabolites that bind to DNA in bronchial epithelial cells. Promutagenic and mutagenic metabolites of BzaP were also released into the culture medium. An increase in mutation frequency for ouabain resistance was found in Chinese hamster V-79 cells when they were cocultivated with bronchial explants in the presence ofBzaP. The proximate carcinogenic form of BzaP, the 7,8-diol ((+-)-r7,t8-dihydroxy-7,8-dihydrobenzo(a)pyrene), was 5-fold more potent as a promutagen than the parent compound. Neither BzaP nor the 7,8-diol increased the mutation frequency in V-79 cells when they were cultured without bronchial explants. The mutation frequency was directly related to the binding levels of BzaP to bronchial DNA and the concentration of either BzaP or the 7,8-diol in the medium.

OSTI ID:
6829581
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 75:4; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL MODELS
BRONCHI
CARCINOGENESIS
CARCINOGENS
CELL CULTURES
CHEMICAL ACTIVATION
CHEMICAL BONDS
CLONE CELLS
CONDENSED AROMATICS
DNA
HAMSTERS
HYDROCARBONS
MAMMALS
MAN
METABOLISM
METABOLITES
MUTAGENESIS
MUTAGENS
MUTATION FREQUENCY
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
POLYCYCLIC AROMATIC HYDROCARBONS
PRIMATES
RESPIRATORY SYSTEM
RESPIRATORY TRACT CELLS
RODENTS
VERTEBRATES