Fidder A, Moes G W, Scheffer A G, van der Schans G P, Baan R A, de Jong L P, Benschop H P
TNO Prins Maurits Laboratory, Rijswijk, The Netherlands.
Chem Res Toxicol. 1994 Mar-Apr;7(2):199-204. doi: 10.1021/tx00038a013.
As part of a program to develop methods for verification of alleged exposure to sulfur mustard, we synthesized and characterized the adducts most likely formed by alkylation of DNA with sulfur mustard: N7-[2-[(2-hydroxyethyl)thio]ethyl]guanine (1), bis[2-(guanin-7-yl)ethyl] sulfide (2), N3-[2-[(2-hydroxyethyl)thio]ethyl]adenine (3), and O6-[2-[(2-hydroxyethyl)thio]ethyl]-guanine and its 2'-deoxyguanosine derivative. Incubation of double-stranded calf thymus DNA and human blood with [35S]sulfur mustard in vitro followed by enzymatic degradation of the DNA and mild depurination afforded three major radioactive peaks upon HPLC analysis. These peaks were identified as 1-3 by coelution with the synthetic markers and mass spectrometric and electronic spectra. Compound 1 appeared to be the most abundant adduct, which is in agreement with previous investigations on DNA alkylation with sulfur mustard.
作为开发用于验证疑似接触硫芥方法的项目的一部分，我们合成并表征了最有可能由硫芥与DNA烷基化形成的加合物：N7-[2-[(2-羟乙基)硫代]乙基]鸟嘌呤(1)、双[2-(鸟嘌呤-7-基)乙基]硫化物(2)、N3-[2-[(2-羟乙基)硫代]乙基]腺嘌呤(3)以及O6-[2-[(2-羟乙基)硫代]乙基]鸟嘌呤及其2'-脱氧鸟苷衍生物。将双链小牛胸腺DNA和人血液与[35S]硫芥在体外孵育，随后对DNA进行酶促降解并轻度脱嘌呤，经高效液相色谱分析得到三个主要放射性峰。通过与合成标记物共洗脱以及质谱和电子光谱鉴定，这些峰被确定为1 - 3。化合物1似乎是最丰富的加合物，这与先前关于硫芥与DNA烷基化的研究结果一致。
