Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polycyclic aromatic hydrocarbon

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearch

  • Ih Chang Hsu, United States
  • Gary D. Stoner, 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
  • Benjamin F. Trump, United States
  • James K. Selkirk, United States
  • Curtis C. Harris, United States
  • Institute of Environmental and Occupational Medicine
Cultured human bronchial explants activated benzo[alpha]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 of BzaP. The proximate carcinogenic form of BzaP, the 7,8-diol [(+/-)-r7,t8-dihyroxy-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 concentratin of either BzaP or the 7,8-diol in the medium.
Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Pages (from-to)2003-2007
Number of pages5
Publication statusPublished - Apr 1978

See relations at Aarhus University Citationformats

ID: 1239220