Sterigmatocystin-DNA interactions: identification of a major adduct formed after metabolic activation in vitro.
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.
D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism*; D004852:Epoxy Compounds; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013057:Spectrum Analysis; D013241:Sterigmatocystin / Q000031:analogs & derivatives / Q000378:metabolism*; D014966:Xanthenes / Q000378:metabolism*
D004852:Epoxy Compounds; D014966:Xanthenes; D013241:Sterigmatocystin; D004247:DNA