Chipinda Itai, Hettick Justin M, Simoyi Reuben H, Siegel Paul D
Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, USA.
Contact Dermatitis. 2008 Aug;59(2):79-89. doi: 10.1111/j.1600-0536.2008.01399.x.
Zinc diethyldithiocarbamate (ZDEC) and its disulfide, tetraethylthiuram disulfide (TETD), are rubber accelerators and contact allergens that cross-react in some individuals.
This study explored potential protein haptenation mechanisms of ZDEC and its oxidation products.
ZDEC oxidation/reduction products and sites of protein binding were assessed using high-performance liquid chromatography and mass spectrometry. The murine local lymph node assay (LLNA) was employed to probe haptenation mechanisms of ZDEC by examining its allergenicity along with its oxidation products and through elimination of oxidation and chelation mechanisms by substituting cobalt for zinc [cobalt (II) dithiocarbamate, CoDEC].
Oxidation of ZDEC by hypochlorous acid (bleach, HOCl), iodine, or hydrogen peroxide resulted in production of TETD, tetraethylthiocarbamoyl disulfide, and tetraethyldicarbamoyl disulfide (TEDCD). Albumin thiols reduced TETD with subsequent mixed disulfide formation/haptenation. ZDEC directly chelated the copper ion on the active site of the superoxide dismutase, whereas CoDEC did not bind to Cu proteins or form mixed disulfides with free thiols. ZDEC, sodium diethyldithiocarbamate, TEDCD, and TETD were all positive in the LLNA except CoDEC, which was non-allergenic.
The thiol is the critical functional group in ZDEC's allergenicity, and haptenation is predominantly through chelation of metalloproteins and formation of mixed disulfides.
二乙基二硫代氨基甲酸锌（ZDEC）及其二硫化物，四乙基秋兰姆二硫化物（TETD），是橡胶促进剂和接触性过敏原，在一些个体中会发生交叉反应。
本研究探讨了ZDEC及其氧化产物潜在的蛋白质半抗原化机制。
使用高效液相色谱和质谱评估ZDEC的氧化/还原产物及蛋白质结合位点。采用小鼠局部淋巴结试验（LLNA），通过检测ZDEC及其氧化产物的致敏性，并通过用钴替代锌[二硫代氨基甲酸钴（II），CoDEC]消除氧化和螯合机制，来探究ZDEC的半抗原化机制。
次氯酸（漂白剂，HOCl）、碘或过氧化氢对ZDEC的氧化导致生成TETD、四乙基硫代氨基甲酰二硫化物和四乙基二氨基甲酰二硫化物（TEDCD）。白蛋白硫醇还原TETD，随后形成混合二硫化物/半抗原化。ZDEC直接螯合超氧化物歧化酶活性位点上的铜离子，而CoDEC不与铜蛋白结合，也不与游离硫醇形成混合二硫化物。ZDEC、二乙基二硫代氨基甲酸钠、TEDCD和TETD在LLNA中均呈阳性，除CoDEC无致敏性外。
硫醇是ZDEC致敏性中的关键官能团，半抗原化主要通过金属蛋白的螯合和混合二硫化物的形成。
