Metabolism of (/sup 3/H)benzo(a)pyrene by cultured human bronchus and cultured human pulmonary alveolar macrophages

Journal Article · Wed Mar 01 04:00:00 EST 1978 · Lab. Invest.; (United States)

OSTI ID:6751090

Autrup, H; Harris, C C; Stoner, G D; Selkirk, J K; Schafer, P W; Trump, B F

The metabolism of (/sup 3/H)benzo(a)pyrene by cultured human bronchial epithelium and pulmonary alveolar macrophages was studied. Explants of bronchus were prepared and pulmonary alveolar macrophages were isolated from peripheral lung by trypsinization and by differential adhesion to plastic tissue culture dishes. After 7 days in culture the bronchus explant and the macrophages were exposed to (/sup 3/H)benzo(a)pyrene, and the binding to cellular macromolecules was studied. Aryl hydrocarbon hydroxylase activity was determined by the release of tritiated water into the culture medium from metabolized (/sup 3/H)benzo(a)pyrene. Variation in the binding level of benzo(a)pyrene to DNA and to protein in macrophages from different individuals showed 9- and 33-fold interindividual variation, respectively. In the macrophages, both binding of benzo(a)pyrene to macromolecules and aryl hydrocarbon hydroxylase activity were dependent on the length of time in culture and length of exposure to benzo(a)pyrene. Pretreatment of the macrophages with benz(..cap alpha..)anthracene increased both binding level of benzo(a)pyrene and aryl hydrocarbon hydroxylase activity. When coincubated with benzo(a)pyrene, cycloheximide, 7,8-benzoflavone, or actinomycin D reduced both level of binding and activity of aryl hydrocarbon hydroxylase. When macrophage cultures were maintained at pO/sub 2/ greater than atmospheric air, an increase in binding level and enzyme activity was found. The major metabolites of benzo(a)pyrene formed by macrophages were 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene (16 to 39%) and two distinct peaks containing unidentified polar metabolites. A negative correction between binding of benzo(a)pyrene to protein and aryl hydrocarbon hydroxylase exists in pulmonary macrophages, but no correlation between data from bronchus and macrophages was found.

• Research Organization: National Insts. of Health, Bethesda, MD
• OSTI ID: 6751090
• Journal Information: Lab. Invest.; (United States), Journal Name: Lab. Invest.; (United States) Vol. 38:3; ISSN LAINA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTINOMYCIN
ANIMAL CELLS
ANIMALS
ANTIBIOTICS
ANTIMITOTIC DRUGS
AROMATICS
BENZOPYRENE
BODY
BRONCHI
CARCINOGENS
CELL CULTURES
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
CRYOGENIC FLUIDS
CYCLOHEXIMIDE
DNA
DRUGS
ELEMENTS
ENZYMES
FLUIDS
FUNGICIDES
HYDROCARBONS
HYDROXYLASE
IN VITRO
LABELLED COMPOUNDS
LUNGS
MACROPHAGES
MAMMALS
MAN
METABOLISM
NONMETALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGEN
PESTICIDES
PHAGOCYTES
PRIMATES
PROTEINS
RESPIRATORY SYSTEM
SOMATIC CELLS
VERTEBRATES