Metabolic activation and DNA binding of benzo(a)pyrene in cultured human bronchus.

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  • Shen K. Yang, United States
  • Harry V. Gelboin, United States
  • Benjamin F. Trump, 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
  • Curtis C. Harris, United States
  • Institute of Environmental and Occupational Medicine
Human bronchus is one target site for the carcinogenic action of tobacco smoke, which contains chemical carcinogens, including benzo(a)pyrene. Human bronchi were obtained from surgery or “immediate” autopsy and then cultured in a chemically defined medium. The cultured bronchi were exposed to either benzo(a)pyrene or its metabolities, and their levels of binding to DNA were measured. One of the benzo(a)pyrene metabolites, (-)-trans-7,8-diol, is more active in binding to DNA than benzo(a)pyrene and several of its metabolites, including (-)-trans-4,5-diol, (-)-trans-9,10-diol, and phenols. The predominant metabolite formed by human bronchus from the (-)-trans-7,8-diol is found by high-pressure liquid chromatographic analysis to be the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahy-drobenzo(a)pyrene. The results suggest that this diol-epoxide is the major benzo(a)pyrene metabolite bound to DNA in human bronchus.
Original languageEnglish
JournalCancer Research
Pages (from-to)1207-1211
Number of pages5
Publication statusPublished - Apr 1977

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