Open AccessSterigmatocystin-DNA interactions: identification of a major adduct formed after metabolic activation in vitro.
Author(s) -
John M. Essigmann,
Lucy Barker,
Kerry W. Fowler,
Manuel Francisco,
Ver N. Reinhold,
Gerald N. Wogan
Publication year - 1979
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.76.1.179
Subject(s) - adduct , sterigmatocystin , guanine , metabolite , chemistry , dna , biochemistry , nucleotide , stereochemistry , dna adduct , organic chemistry , aflatoxin , food science , gene
Sterigmatocystin (ST), a potent hepatocarcinogen, was covalently bound to calf thymus DNA by incubation in the presence of phenobarbital-induced rat liver microsomes. Acid hydrolysis of ST-modified DNA liberated a major guanine-containing adduct, present in DNA at an estimated level of 1 ST residue per 100-150 nucleotides. The adduct was isolated by high-pressure liquid chromatography and subjected to structural analysis. Spectral and chemical data identified the adduct as 1,2-dihydro-2-(N(7)-guanyl)-1-hydroxysterigmatocystin, the guanine and hydroxyl moieties being in a trans configuration. The structure and stereochemistry of this adduct indicated that the exo-ST-1,2-oxide was the metabolite that reacted with DNA, and the quantitative yield of adduct indicated that this metabolite was a major product of the in vitro metabolism of ST.