Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon

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  • 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
  • John M. Essigmann, United States
  • Robert G. Croy, United States
  • Benjamin F. Trump, United States
  • Gerald N. Wogan, United States
  • Curtis C. Harris, United States
  • Institute of Environmental and Occupational Medicine
Aflatoxin B1 and benzo(a)pyrene were activated by both cultured human bronchus and human colon as measured by binding to cellular DNA and protein. The binding of aflatoxin B1 to DNA was dose dependent, and the level of binding was higher in cultured human bronchus than it was in the colon. When compared to aflatoxin B1, the binding level of benzo(a)pyrene to both bronchial and colonic DNA was generally higher. The major adducts formed in both tissues by the interaction of aflatoxin B1 and DNA were chromatographically identical to 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1 (Structure 1) with the guanyl group and hydroxy group in trans-position and an adduct which has been tentatively identified by other investigators as 2,3-dihydro-2-(N5-formyl-2',5',6'-triamino-4'-oxo-N5-pyrimidyl)-3-hydroxyaflatoxin B1 (Structure 11). Seventy % of the radioactivity associated with bronchial DNA was found in these two peaks, and the ratio of radioactivity between the peaks was nearly 1. In colonic DNA, the ratio between Structures 1 and 11 was approximately 2. These observations add aflatoxin B1 to the list of chemical procarcinogens metabolized by cultured human tissues and in which the carcinogen-DNA adducts are similar to the adducts formed in animal tissue susceptible to the carcinogenic action of aflatoxin B1.
Original languageEnglish
JournalCancer Research
Pages (from-to)694-698
Number of pages5
Publication statusPublished - Mar 1979

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