Research by Prof. Stone and co-Workers Illuminates the Replication Bypass of Aflatoxin Adducts in Mammalian Cells
Aflatoxin B 1 (AFB1) is a fungal toxin which is a known carcinogen associated with early-onset hepatocellular carcinoma. Two new reports by Prof. Stone and his collaborator Prof. R. Stephen Lloyd at the Oregon Health & Science University confirm that both AFB1–N7-Gua and AFB1–FAPY are, in fact, highly mutagenic in primate cells into which either an AFB1–N7-Gua- or AFB1–FAPY-containing DNA substrate was introduced. This work has been highlighted in the Spotlight section of the American Chemical Society journal Chemical Research in Toxicology [http://pubs.acs.org/doi/abs/10.1021/tx500300x]. Liang Li, a Ph.D. student in Prof. Stone's laboratory, synthesized a series of site-specific AFB1 lesions that were inserted into primate cells and replicated. The results of this research revealed that these AFB1 lesions were highly mutagenic, yielding replication error frequencies of 97%, with the predominant base substitutions being G to T transversions. These transversions are consistent with mutational data derived from aflatoxin-associated HCCs. The original research articles were published in the Journal of Biological Chemistry and in Carcinogenesis.
Lin, Y-C., Li, L., Burgers, P.M., Stone, M.P., & Lloyd, R.S. "Molecular Basis of Aflatoxin-Induced Mutagenesis – Role of the Aflatoxin B1-Formamidopyrimidine Adduct." (2014) Carcinogenesis 35, 1461-1468. PMID: 24398669 PMCID: in process.
Lin, Y.-C., Li, L., Makarova, A.V, Burgers, P.M., Stone, M.P., & Lloyd, R.S. "Role of the Primary Aflatoxin B1-DNA Adduct (AFB1-N7-Gua) in Aflatoxin-induced Mutagenesis." (2014) J. Biol. Chem. 289, 18497-18506. PMID: 24838242 PMCID: in process.