Identification of adducts formed in the reaction of alpha-acetoxy-N-nitrosopyrrolidine with deoxyribonucleosides and DNA.
Identification of adducts formed in the reaction of alpha-acetoxy-N-nitrosopyrrolidine with deoxyribonucleosides and DNA.
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鉴定 α-乙酰氧基-N-亚硝基吡咯烷与脱氧核糖核苷和 DNA 反应中形成的加合物。
DOI：
10.1021/tx600332p
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发表时间：
2007
影响因子：
4.1
通讯作者：
Hecht,StephenS
中科院分区：
文献类型：
--
作者：
Wang,Mingyao;Lao,Yanbin;Cheng,Guang;Shi,Yongli;Villalta,PeterW;Hecht,StephenS
N-亚硝基吡咯烷（NPYR）是一种公认的大鼠肝癌原。NPYR需要通过细胞色素P450催化的α-羟基化进行代谢活化，以表达其致癌活性。这产生α-羟基NPYR（2），其自发开环为4-氧代丁烷重氮氢氧化物（4），这是一种高度反应性的中间体，其本身可以修饰DNA或产生亲电试剂级联，与DNA反应产生加合物。在该反应中形成的多个dGuo加合物先前已被表征，但没有与其他DNA核碱基形成加合物的实例。在本研究中，我们使用α-乙酰氧基NPYR（3）作为2和4的稳定前体。使化合物3与DNA反应。将DNA酶解为脱氧核糖核苷，产物用LC-ESI-MS和LC-ESI-MS/MS分析。产物经MS、UV和NMR谱鉴定为N6-（四氢呋喃-2-基）dAdo（16）和N4-（四氢呋喃-2-基）dCyd（17），以及先前表征的N2-（四氢呋喃-2-基）dGuo（13）。也形成了不稳定的dThd加合物。通过NaBH 3CN还原3与脱氧核苷或DNA的反应混合物，进一步表征了加合物。这产生N6-（4-羟基丁-1-基）dAdo（21）、N4-（4-羟基丁-1-基）dCyd（22）、O2-（4-羟基丁-1-基）dThd（23）、O 4-（4-羟基丁-1-基）dThd（24）和3-（4-羟基丁-1-基）dThd（25）。加合物21和22通过其光谱特性进行表征，而dThd加合物23 − 25通过与合成标准品进行比较来鉴定。本研究结果表明，除了先前表征的dGuo加合物外，3还与DNA中的dAdo、dCyd和dThd形成加合物。这些新表征的标准品可用于研究用NPYR处理的大鼠中的DNA加合物形成。
N-Nitrosopyrrolidine (NPYR) is a well-established hepatocarcinogen in the rat. NPYR requires metabolic activation by cytochrome P450-catalyzed α-hydroxylation to express its carcinogenic activity. This produces α-hydroxyNPYR (2), which spontaneously ring opens to 4-oxobutanediazohydroxide (4), a highly reactive intermediate, which may itself modify DNA or yield a cascade of electrophiles that react with DNA to produce adducts. Multiple dGuo adducts formed in this reaction have been previously characterized, but there are no examples of adducts formed with other DNA nucleobases. In this study, we used α-acetoxyNPYR (3) as a stable precursor to2and4. Compound3was allowed to react with DNA. The DNA was enzymatically hydrolyzed to deoxyribonucleosides, and the products were analyzed by LC-ESI-MS and LC-ESI-MS/MS. Reactions of3with individual deoxyribonucleosides were also carried out. The products were identified by their MS, UV, and NMR spectra asN6-(tetrahydrofuran-2-yl)dAdo (16) andN4-(tetrahydrofuran-2-yl)dCyd (17) in addition to the previously characterizedN2-(tetrahydrofuran-2-yl)dGuo (13). Unstable dThd adducts were also formed. Further characterization of the adducts was achieved by NaBH3CN reduction of the reaction mixtures of3with deoxyribonucleosides or DNA. This producedN6-(4-hydroxybut-1-yl)dAdo (21),N4-(4-hydroxybut-1-yl)dCyd (22),O2-(4-hydroxybut-1-yl)dThd (23),O4-(4-hydroxybut-1-yl)dThd (24), and 3-(4-hydroxybut-1-yl)dThd (25). Adducts21and22were characterized by their spectral properties, while the dThd adducts23−25were identified by comparison to synthetic standards. The results of this study demonstrate that3forms adducts with dAdo, dCyd, and dThd in DNA, in addition to the previously characterized dGuo adducts. These newly characterized standards can be used to investigate DNA adduct formation in rats treated with NPYR.
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食品和饮料中的预制 N-亚硝基化合物。
DOI：
--
发表时间：
1989
期刊：
Cancer surveys
影响因子：
--
作者：
Hotchkiss,JH
通讯作者：
Hotchkiss,JH
血吸虫病和血吸虫膀胱癌患者尿液中硝酸盐、亚硝酸盐和 N-亚硝基化合物的排泄。
影响因子：
4.7
作者：
A. Tricker;Mostafa H. Mostafa;Bertold Spiegelhalder;R. Preussmann
通讯作者：
R. Preussmann
埃及血吸虫和曼氏血吸虫感染患者尿液中的硝酸盐、亚硝酸盐和挥发性N-亚硝基化合物。
影响因子：
4.7
作者：
M. H. Mostafa;S. Helmi;A. Badawi;A. Tricker;B. Spiegelhalder;R. Preussmann
通讯作者：
R. Preussmann
鉴定巴豆醛为致癌物 N-亚硝基吡咯烷的 α-羟基化形成的肝微粒体代谢物。
影响因子：
4.1
作者：
M. Wang;F. Chung;S. Hecht
通讯作者：
S. Hecht
用 α-乙酰氧基-N-亚硝基吡咯烷或巴豆醛处理的 DNA 水解产物中的乳醇
DOI：
--
发表时间：
1998
期刊：
影响因子：
--
作者：
Mingyao Wang;P. Upadhyaya;T. T. Dinh;L. Bonilla;S. Hecht
通讯作者：
S. Hecht