柄曲霉素与DNA的相互作用：体外代谢活化后形成的主要加合物的鉴定。
Sterigmatocystin-DNA interactions: identification of a major adduct formed after metabolic activation in vitro.
作者信息
Essigmann J M, Barker L J, Fowler K W, Francisco M A, Reinhold V N, Wogan G N
出版信息
Proc Natl Acad Sci U S A. 1979 Jan;76(1):179-83. doi: 10.1073/pnas.76.1.179.
Abstract
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.
摘要
柄曲霉素（ST）是一种强效肝癌致癌物，在苯巴比妥诱导的大鼠肝微粒体存在的情况下孵育，它会与小牛胸腺DNA共价结合。对ST修饰的DNA进行酸水解，释放出一种主要的含鸟嘌呤加合物，该加合物在DNA中的估计水平为每100 - 150个核苷酸中有1个ST残基。通过高压液相色谱法分离该加合物并进行结构分析。光谱和化学数据确定该加合物为1,2 - 二氢 - 2 -（N（7）-鸟嘌呤基）- 1 - 羟基柄曲霉素，鸟嘌呤和羟基部分呈反式构型。该加合物的结构和立体化学表明，外 - ST - 1,2 - 环氧化物是与DNA反应的代谢物，加合物的定量产率表明该代谢物是ST体外代谢的主要产物。
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