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Metabolism of Aflatoxin B₁ and Identification of the Major Aflatoxin B₁-DNA Adducts Formed in Cultured Human Bronchus and Colon¹

Human Tissue Studies Section, Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20014 [H. A., C. C. H.]; Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 [J. M. E., R. G. C., G. N. W.]; and Department of Pathology, University of Maryland Medical School, Baltimore, Maryland 21201 [B. F. T.]

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 I) 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 II). Seventy % of the radio-activity 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 I and II 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.

¹ This work was supported in part by Contracts N01-CP 43265 and N01-CP-43237 from the NIH.

² To whom request for reprints should be addressed.

Received 7/14/78. Accepted 11/14/78.

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