Briggs Mary K, Desavis Emmanuel, Mazzer Paula A, Sunoj R B, Hatcher Susan A, Hadad Christopher M, Hatcher Patrick G
Department of Chemistry, The Ohio State University, Columbus, Ohio, 43210, USA.
Chem Res Toxicol. 2003 Nov;16(11):1484-92. doi: 10.1021/tx0341512.
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are converted to cytotoxic and carcinogenic metabolites, quinones, by detoxifying enzyme systems in animals. PAH metabolites such as the quinones can form Michael adducts with biological macromolecules containing reactive nucleophiles, making detection of exposure to PAHs difficult using conventional techniques. A technique has been developed for detecting exposure to PAHs. Tetramethylammonium hydroxide (TMAH) thermochemolysis coupled with GC/MS is proposed as an assay method for PAH quinones that have formed Michael adducts with biological molecules. Three PAH quinones (1,4-naphthoquinone, 1,2-naphthoquinone, and 1,4-anthraquinone) and 1,4-benzoquinone were reacted with cysteine, and the TMAH thermochemolysis method was used to assay for both thiol and amine adduction between the quinones and the cysteine. Additional studies with 1,4-naphthoquinone adducts to glutathione and bovine serum albumin showed the same thiol and amine TMAH thermochemolysis products with larger peptides as was observed with cysteine adducts. The TMAH GC/MS method clearly shows great promise for detecting PAH quinones, produced by enzymatic conversion of PAHs in biological systems, that have been converted to respective Michael adducts.
多环芳烃（PAHs）是环境污染物，在动物体内会被解毒酶系统转化为具有细胞毒性和致癌性的代谢产物醌类。醌类等PAH代谢产物可与含有反应性亲核试剂的生物大分子形成迈克尔加成物，这使得使用传统技术检测PAH暴露变得困难。现已开发出一种检测PAH暴露的技术。氢氧化四甲铵（TMAH）热化学裂解结合气相色谱/质谱法被提议作为检测已与生物分子形成迈克尔加成物的PAH醌类的分析方法。三种PAH醌类（1,4-萘醌、1,2-萘醌和1,4-蒽醌）以及1,4-苯醌与半胱氨酸反应，并用TMAH热化学裂解方法检测醌类与半胱氨酸之间的硫醇和胺加成反应。对1,4-萘醌与谷胱甘肽和牛血清白蛋白加成物的进一步研究表明，与半胱氨酸加成物相比，较大肽段的硫醇和胺TMAH热化学裂解产物相同。TMAH气相色谱/质谱法在检测生物系统中PAHs酶促转化产生的、已转化为各自迈克尔加成物的PAH醌类方面显然具有很大的前景。
