DNA conformation mediates aflatoxin B1-DNA binding and the formation of guanine N7 adducts by aflatoxin B1 8,9-exo-epoxide

Chem Res Toxicol. Jan-Feb 1993;6(1):64-8. doi: 10.1021/tx00031a010.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aflatoxin B1 / analogs & derivatives*
  • Aflatoxin B1 / chemistry*
  • Base Sequence
  • DNA / chemistry*
  • DNA Adducts*
  • DNA, Single-Stranded / chemistry
  • Guanine / chemistry*
  • Intercalating Agents / chemistry
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Polymers

Substances

  • DNA Adducts
  • DNA, Single-Stranded
  • Intercalating Agents
  • Polymers
  • aflatoxin B1-DNA adduct
  • aflatoxin B1-2,3-oxide
  • Guanine
  • DNA
  • Aflatoxin B1