DNA conformation mediates aflatoxin B1-DNA binding and the formation of guanine N7 adducts by aflatoxin B1 8,9-exo-epoxide.
The binding of aflatoxin B1 to DNA and DNA adduction by aflatoxin B1 exo-8,9-epoxide were studied as a function of DNA conformation. Equilibrium binding of aflatoxin B1 to A-, B-, and Z-form helices was monitored by measurement of NMR linewidth for the methoxy protons of aflatoxin B1. The data revealed that as compared to B-form DNA, the association of aflatoxin with the A-form helix is significantly reduced. No binding to Z-DNA was observed. The yields obtained following reaction of the respective monomers with aflatoxin B1 exo-8,9-epoxide revealed that only dG forms an adduct. The reactivity of aflatoxin B1 exo-8,9-epoxide with single-strand DNA was determined via constant-temperature experiments in which the yield of adduct was measured for a family of oligonucleotides of increasing thermal stability. The results demonstrate that duplex structure favors adduct formation. Adduct yields were compared for A-, B-, and Z-form helices. About 12 times less adduct is produced from the A-form helix as compared to B-form, while no adduct is produced from a Z-form duplex. The results support the conclusion that reaction of aflatoxin B1 exo-8,9-epoxide with DNA proceeds via an intercalated transition-state complex only with the B-form double helix.
Raney
V M
VM
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Harris
T M
TM
Stone
M P
MP
D016604:Aflatoxin B1 / Q000031:analogs & derivatives* / Q000737:chemistry*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts; D004277:DNA, Single-Stranded / Q000737:chemistry; D006147:Guanine / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011108:Polymers
D018736:DNA Adducts; D004277:DNA, Single-Stranded; D007364:Intercalating Agents; D011108:Polymers; C072611:aflatoxin B1-DNA adduct; C006426:aflatoxin B1-2,3-oxide; D006147:Guanine; D004247:DNA; D016604:Aflatoxin B1