Habraken Y, Carter C A, Kirk M C, Riordan J M, Ludlum D B
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Carcinogenesis. 1990 Feb;11(2):223-8. doi: 10.1093/carcin/11.2.223.
HPLC analyses of the bases released by acid from N-(2-chloroethyl)-N-nitrosourea-treated DNA and N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea-treated DNA show the presence of a new guanine adduct, N2,3-ethanoguanine. This derivative can be synthesized at the monomer level by treating 2-hydroxyethylguanine with thionyl chloride. The product of this reaction, purified by HPLC, has been shown to have a mol. wt corresponding to ethanoguanine by mass spectrometry; NMR spectrometry also supports this structural assignment. The UV and fluorescence spectra are very similar to those of N2,3-ethenoguanine, providing evidence that the ethano bridge is attached between N2 and 3 positions. Proof that the derivative is N2,3-ethanoguanine comes from the fact that it can be converted to N2,3-ethenoguanine by dehydrogenation on a palladium catalyst. The discovery of this new derivative raises to four the number of tricylic derivatives that have been isolated from DNA treated with 2-haloethylnitrosoureas. The new adduct, N2,3-ethanoguanine, is closely related to an etheno adduct formed by chloroacetaldehyde, a metabolite of the human carcinogen vinyl chloride, and may have relevance to either the therapeutic or carcinogenic actions of the 2-haloethylnitrosoureas.
对经N-(2-氯乙基)-N-亚硝基脲处理的DNA和经N-(2-氯乙基)-N'-环己基-N-亚硝基脲处理的DNA用酸释放出的碱基进行的高效液相色谱分析表明存在一种新的鸟嘌呤加合物，即N2,3-乙醇基鸟嘌呤。该衍生物可通过用亚硫酰氯处理2-羟乙基鸟嘌呤在单体水平上合成。通过高效液相色谱纯化的该反应产物，经质谱分析显示其分子量与乙醇基鸟嘌呤相对应；核磁共振光谱也支持这一结构归属。紫外光谱和荧光光谱与N2,3-乙烯基鸟嘌呤的光谱非常相似，这证明乙醇基桥连接在N2和3位之间。该衍生物为N2,3-乙醇基鸟嘌呤的证据来自于它可通过在钯催化剂上脱氢转化为N2,3-乙烯基鸟嘌呤这一事实。这种新衍生物的发现使从用2-卤代乙基亚硝基脲处理的DNA中分离出的三环衍生物的数量增加到了四种。新的加合物N2,3-乙醇基鸟嘌呤与由人类致癌物氯乙烯的代谢产物氯乙醛形成的乙烯基加合物密切相关，并且可能与2-卤代乙基亚硝基脲的治疗作用或致癌作用有关。
