Olsen Raymond, Backman Josefin, Molander Paal, Øvrebø Steinar, Thorud Syvert, Lundanes Elsa, Greibrokk Tyge, Kronberg Leif
National Institute of Occupational Health, P.O. Box 8149 Dep., N-0033 Oslo, Norway.
Chem Res Toxicol. 2007 Jun;20(6):965-74. doi: 10.1021/tx7000477. Epub 2007 May 23.
Glutaraldehyde (1,5-pentanedial) is a widely used industrial chemical that has been found to be mutagenic in bacteria and mammalian cells. In this study, we examined the reaction of glutaraldehyde with 2'-deoxyadenosine and calf thymus DNA in aqueous buffered solutions. The 2'-deoxyadenosine adducts were isolated by reversed phase HPLC and characterized by their UV absorbance and 1H and 13C NMR spectroscopic and mass spectrometric features. The reaction produced three major adducts. The adduct dA567 was derived from two 2'-deoxyadenosine units bound together with a piperidine unit, and its yield was 10.4%. The carbons of the piperidine ring originated from glutaraldehyde, whereas the nitrogen of the ring originated from the exocyclic amino group of one of the 2'-deoxyadenosine units. The adduct dA451d (yield 0.6%) was similar in structure to dA567, but one of the deoxyribose moieties from 2'-deoxyadenosine was missing. The third adduct, dA334, consisted of a hydroxy-tetrahydropyridine moiety derived from glutaraldehyde and N6 of 2'-deoxyadenosine (yield 4.0%). Furthermore, LC-ESI-MS/MS analysis of the reaction mixture revealed the formation of compounds with ion peaks of m/z = 352. None of these compounds were sufficiently stable for preparative isolation. They were tentatively identified as a pair of diastereomers of 2,6-dihydroxypiperidine derivatives, which are likely precursors to dA334. Plausible mechanisms for the formation of the adducts are presented. In the reaction of glutaraldehyde with single and double stranded calf thymus DNA, the dA334 adduct was formed.
戊二醛（1,5 - 戊二醛）是一种广泛使用的工业化学品，已被发现对细菌和哺乳动物细胞具有致突变性。在本研究中，我们研究了戊二醛在水性缓冲溶液中与2'-脱氧腺苷和小牛胸腺DNA的反应。通过反相高效液相色谱法分离2'-脱氧腺苷加合物，并通过其紫外吸收、1H和13C核磁共振光谱以及质谱特征进行表征。该反应产生了三种主要加合物。加合物dA567由两个通过哌啶单元连接在一起的2'-脱氧腺苷单元组成，其产率为10.4%。哌啶环的碳源自戊二醛，而环的氮源自其中一个2'-脱氧腺苷单元的环外氨基。加合物dA451d（产率0.6%）在结构上与dA567相似，但2'-脱氧腺苷的一个脱氧核糖部分缺失。第三种加合物dA334由源自戊二醛的羟基 - 四氢吡啶部分和2'-脱氧腺苷的N6组成（产率4.0%）。此外，对反应混合物的液相色谱 - 电喷雾串联质谱分析显示形成了离子峰为m/z = 352的化合物。这些化合物均不够稳定，无法进行制备性分离。它们被初步鉴定为一对2,6 - 二羟基哌啶衍生物的非对映异构体，可能是dA334的前体。本文提出了加合物形成的合理机制。在戊二醛与单链和双链小牛胸腺DNA的反应中，形成了dA334加合物。
