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

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  • Herman Autrup
  • C.C. Harris, United States
  • G.D. Stoner, United States
  • J.K. Selkirk, United States
  • B.F. Trump, United States
  • Institute of Environmental and Occupational Medicine
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.
Original languageEnglish
JournalLaboratory Investigation
Pages (from-to)217-224
Number of pages8
Publication statusPublished - 1 Mar 1978

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