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 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.
D016604:Aflatoxin B1 / Q000031:analogs & derivatives; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013950:Thymus Gland / Q000378:metabolism*
D000348:Aflatoxins; D002273:Carcinogens; D006147:Guanine; C028319:2,3-dihydro-2-(N(7)-guanyl)-3-hydroxyaflatoxin B1; D004247:DNA; D016604:Aflatoxin B1