Leuratti C, Jones N J, Marafante E, Peltonen K, Kostiainen R, Waters R
Molecular Biology Research Group, School of Biological Sciences, University College of Swansea, Wales, United Kingdom.
IARC Sci Publ. 1993(127):143-50.
1,2-Epoxy-3-butene and 1,2:3,4-diepoxybutane, the two oxidative metabolites of 1,3-butadiene, are considered to be involved in some of the carcinogenicity of the parent compound. Diepoxybutane is a bifunctional alkylating agent and reacts with DNA to form monoadducts and cross-links. We investigated DNA alkylation after exposure to diepoxybutane in order to develop a method for human biomonitoring. After reacting dAMP and then poly(dA-dT) (dA-dT) with diepoxybutane, we identified a major adenine adduct. Preliminary mass spectrometry indicated an adenine adducted by diepoxybutane at the N6 position. A high-performance liquid chromatography/32P-postlabelling method was developed, and the adduct was detected in calf thymus DNA and in DNA from Chinese hamster cells after exposure to diepoxybutane. The labelling efficiency, the amount of the adduct and its stability suggest that it could be a suitable indicator of exposure to butadiene.
1,2-环氧-3-丁烯和1,2:3,4-二环氧丁烷是1,3-丁二烯的两种氧化代谢产物，被认为与母体化合物的某些致癌性有关。二环氧丁烷是一种双功能烷化剂，可与DNA反应形成单加合物和交联。我们研究了暴露于二环氧丁烷后的DNA烷化情况，以便开发一种人体生物监测方法。使dAMP然后聚（dA-dT）（dA-dT）与二环氧丁烷反应后，我们鉴定出一种主要的腺嘌呤加合物。初步质谱分析表明，腺嘌呤在N6位置被二环氧丁烷加合。开发了一种高效液相色谱/ 32P后标记方法，在暴露于二环氧丁烷后的小牛胸腺DNA和中国仓鼠细胞的DNA中检测到了该加合物。标记效率、加合物的量及其稳定性表明，它可能是丁二烯暴露的合适指标。
