Structural Characterization of the Major Adducts Obtained after Reaction of an Ultimate Carcinogen Aflatoxin B₁-Dichloride with Calf Thymus DNA in Vitro

The major adduct formed on acid hydrolysis of calf thymus DNA which has been reacted with 8,9-dichloro-8,9-dihydroaflatoxin B₁, a chemical model of the ultimate carcinogen 8,9-dihydro-8,9-epoxyaflatoxin B₁ (AFB₁-epoxide), has been characterized by proton nuclear magnetic resonance and fast atom bombardment mass spectroscopy. This adduct has been identified as an N7-substituted guanine adduct analogous to that formed on reaction of AFB₁-8,9-epoxide with DNA in vivo and in vitro, namely trans-8,9-dihydro-8-(7-guanyl)-9-hydroxy AFB₁. This 8,9-dichloro-8,9-dihydroaflatoxin B₁ adduct in DNA, like its equivalent AFB₁-epoxide adduct, is prone to quantitative imidazole ring opening of the substituted guanine in mildly alkaline conditions and to substantial depurination under mildly acidic conditions.