Molecular basis of aflatoxin-induced mutagenesis-role of the aflatoxin B1-formamidopyrimidine adduct

Carcinogenesis. 2014 Jul;35(7):1461-8. doi: 10.1093/carcin/bgu003. Epub 2014 Jan 7.


Aflatoxin B1 (AFB1) is a known carcinogen associated with early-onset hepatocellular carcinoma (HCC) and is thought to contribute to over half a million new HCCs per year. Although some of the fundamental risk factors are established, the molecular basis of AFB1-induced mutagenesis in primate cells has not been rigorously investigated. To gain insights into genome instability that is produced as a result of replicating DNAs containing AFB1 adducts, site-specific mutagenesis assays were used to establish the mutagenic potential of the persistent ring-opened AFB1 adduct, AFB1-formamidopyrimidine (AFB1-FAPY). This lesion was highly mutagenic, yielding replication error frequencies of 97%, with the predominant base substitution being a G to T transversion. This transversion is consistent with previous mutational data derived from aflatoxin-associated HCCs. In vitro translesion synthesis assays demonstrated that polymerase (pol) ζ was the most likely candidate polymerase that is responsible for the G to T mutations induced by this adduct.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aflatoxin B1 / adverse effects*
  • Animals
  • COS Cells
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Chlorocebus aethiops
  • DNA Adducts / adverse effects*
  • DNA Replication / genetics*
  • DNA, Single-Stranded / genetics
  • Humans
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Mutagenesis, Site-Directed
  • Mutation / genetics*
  • Polymerase Chain Reaction
  • Pyrimidines / adverse effects*


  • DNA Adducts
  • DNA, Single-Stranded
  • Pyrimidines
  • aflatoxin B1-formamidopyrimidine
  • Aflatoxin B1