Zhu Peijuan, Lee Seon Hwa, Wehrli Suzanne, Blair Ian A
Center for Cancer Pharmacology, University of Pennsylvania School of Medicine, 854 BRB II/III, Philadelphia, 19104-6160, USA.
Chem Res Toxicol. 2006 Jun;19(6):809-17. doi: 10.1021/tx0600189.
Five major products (adducts A(1a), A(1b), A(2), A(3,) and B) from the reaction of guanosine (Guo) with 4-oxo-2(E)-nonenal (ONE) were detected by liquid chromatography-mass spectrometry (LC-MS). Tandem MS (MS/MS) analysis of these compounds suggested that modifications to the nucleoside had been introduced. Adducts A(1a), A(1b), A(2), and A(3) were heptanone-ethano-2'-Guo adducts that all decomposed to adduct B. Adducts A(1a) and A(1b) were isomeric hemi-ketal forms. Adducts A(2) and A(3) were diastereomers of the open chain ketone form. The structure of adduct B was shown by LC-MS/MS and NMR spectroscopy to be the heptanone-etheno-Guo (HepsilonGuo) adduct, 3-(D-erythropentafuranosyl)imidazo-7-(heptane-2' '-one)-9-hydroxyl[1,2-alpha]purine. The overall reaction of Guo with ONE was very similar to its reaction with 2'-deoxyguanosine. Reaction of ONE with yeast transfer RNA also resulted in the formation of HepsilonGuo. Finally, HepsilonGuo was detected and quantified in the RNA from rat intestinal epithelial cells that stably express cyclooxygenase-2. These data show that RNA is modified by the same bifunctional reactive electrophiles derived from lipid peroxidation that covalently modify DNA.
通过液相色谱 - 质谱联用仪（LC - MS）检测到鸟苷（Guo）与4 - 氧代 - 2（E） - 壬烯醛（ONE）反应产生的五种主要产物（加合物A(1a)、A(1b)、A(2)、A(3)和B）。对这些化合物进行串联质谱（MS/MS）分析表明，核苷已发生修饰。加合物A(1a)、A(1b)、A(2)和A(3)是庚酮 - 乙醇 - 2'-Guo加合物，它们都会分解为加合物B。加合物A(1a)和A(1b)是异构的半缩酮形式。加合物A(2)和A(3)是开链酮形式的非对映异构体。通过LC - MS/MS和核磁共振光谱表明，加合物B的结构为庚酮 - 乙烯基 - Guo（HεGuo）加合物，即3 - （D - 赤藓糖基）咪唑并 - 7 - （庚烷 - 2'' - 酮）-9 - 羟基[1,2 - α]嘌呤。Guo与ONE的总体反应与其与2'-脱氧鸟苷的反应非常相似。ONE与酵母转移RNA的反应也导致形成HεGuo。最后，在稳定表达环氧化酶 - 2的大鼠肠上皮细胞的RNA中检测并定量了HεGuo。这些数据表明，RNA会被源自脂质过氧化的相同双功能活性亲电试剂修饰，这些亲电试剂会共价修饰DNA。
