Metabolism of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in cultured human bronchus and pancreatic duct

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  • Curtis C. Harris, United States
  • Herman Autrup, Human Tissue Studies Section, Experimental Pathology Branch, Division of Cancer Cause and Prevention, NCI, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Maryland, Denmark
  • Gary Stoner, United States
  • Shen K. Yang, United States
  • Janet C: Leutz, United States
  • Harry V. Gelboin, United States
  • James K. Selkirk, United States
  • Robert J. Connor, United States
  • Lucy A. Barrett, United States
  • Raymond T. Jones, United States
  • Elizabeth McDowell, United States
  • Benjamin F. Trump, United States
  • Institute of Environmental and Occupational Medicine
The metabolism of two carcinogenic polynuclear aro matic hydrocarbons, benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene, was studied in expiants of human pancreatic duct and bronchus cultured in a chemically defined medium. In cultured human bronchial mucosa, activity of aryl hydrocarbon hydroxylase was inducible by both benz[a]anthracene and BP. Prior exposure of the bronchial expiants to benz[a]anthracene altered the qualitative features of the metabolite profile of BP as analyzed by highpressure liquid chromatography. The metabolite profiles of BP produced by normal-appearing bronchi from patients with lung cancer were also compared with those from patients without lung cancer. The profiles were similar except for an observed higher percentage of organic solvent-extractable metabolites formed by bronchi from the noncancer patients that eluted from the column as a single peak. This peak cochromatographed with both the 9,10-diol and a triol of BP. 7,12-Dimethylbenz[a]anthracene was bound to the DMA of cultured human bronchial cells at higher levels than was BP. Binding of 7,12-dimethylbenz[a]anthracene to DMA in human pancreatic duct was consistently less than that in cultured bronchi in the 5 patients studied. Human pancreatic duct and bronchus have the capacity to activate polynuclear aromatic hydrocarbons into metabolic intermediates that bind to DMA and, presumably, into ultimate carcinogens.
Original languageEnglish
JournalCancer Research
Pages (from-to)3349-3353
Number of pages5
Publication statusPublished - Sep 1977

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