Metabolism of Aflatoxin B1and Identification of the Major Aflatoxin B1-DNA Adducts Formed in Cultured Human Bronchus and Colon1

Aflatoxin B, 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 B, 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 B,, 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 B, (Structure I) with the guanyl group and hydroxy group in trans-position and an adduct which has been tentatively identified by other investigators as 2,3dihydro-2-(N5-formyl-2' ,5' ,6'-tniamino-4'-oxo-N5-pyrimidyl)3-hydroxyaflatoxin B, (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 B, to the list of chemical procarcinogens metabo lized by cultured human tissues and in which the carcino gen-DNA adducts are similar to the adducts formed in animal tissue susceptible to the carcinogenic action of aflatoxin B1.