title: Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro.
abstract: The covalent binding of the hepatocarcinogen aflatoxin B1 by rat liver microsomes to calf thymus DNA resulted in a binding level equal to one aflatoxin residue per 60 DNA nucleotides. An aflatoxin derivative-guanine adduct was efficiently liberated from DNA with formic acid. Analytical reversed-phase high-pressure liquid chromatography of the DNA hydrolysate revealed that approximately 90% of the carcinogen bound to DNA could be accounted for as a single component. Preparative high-pressure liquid chromatography was used to isolate sufficient quantities of the adduct for structural analysis from large quantities (340 mg) of DNA. A combination of spectral and chemical data indicates that the major product of the interaction of metabolically activated aflatoxin B1 and DNA is 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1 with the guanine and hydroxyl functions possessing a trans configuration. The structural data support the hypothesis that the putative 2,3-oxide of aflatoxin B1 is quantitatively important as an intermediate in the binding of aflatoxin B1 to nucleic acids.
mesh_terms: D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000348:Aflatoxins; D006147:Guanine; D004247:DNA
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