MYELOPEROXIDASE ACTIVATION OF N ACETYLBENZIDINE

在接触联苯胺的工人中， N‘-(3’-单磷-脱氧鸟苷-8-基)-N-乙酰基联苯胺(1A) 在膀胱脱落细胞和外周血白细胞中检测到。 由于这两种细胞都表现出显著的过氧化活性，这一点 被认为是N-乙酰基联苯胺活化的可能机制 (ABZ)。为此，~3H-ABZ的髓过氧化物酶(MPO)代谢 (0.06 mm)，用高效液相色谱法进行分析。实质性新陈代谢 观察到MPO对ABZ的影响，并诱导了2倍的增加 在反应混合物中加入100 mM的氯化钠。牛磺酸(10毫米) 在有氯化钠存在的情况下代谢降低，但在没有氯化钠的情况下没有。 叠氮(1 Mm)、氰化物(10 Mm)和抗坏血酸(1 Mm) 抑制新陈代谢。与谷胱甘肽(0.1 mM)一起，一种新的代谢物 观察对(-谷氨酰转肽酶)和 用温和的酸或碱处理(0.1N HCl或0.1N)将其水解为ABZ 氢氧化钠10分钟)。在DGP、MPO或0.3 mm NAOC L在场的情况下 生产的 加合物一种加合物，其形成因以下两种情况之一的存在而被阻止 谷胱甘肽或维生素C ESI/MS/MS分析证明了该加合物 到了1a。因此，ABZ是MPO的还原共底物和 OCL-的还原剂。MPO可能对ABZ的激活负责 由外周白血球形成1A。

In workers exposed to benzidine, N'-(3'-monophospho-deoxyguanosin-8 -yl)-N-acetylbenzidine (1A) was detected in exfoliated bladder cells and peripheral white blood cells. Because both cell types exhibit substantial peroxidatic activity, this was considered a likely mechanism for activation of N-acetylbenzidine (ABZ). For this reason, myeloperoxidase (MPO) metabolism of 3H-ABZ (0.06 mM) was assessed with analysis by HPLC. Substantial metabolism of ABZ by MPO was observed with a 2-fold increase elicited by inclusion of 100 mM NaCl in the reaction mixture. Taurine (10 mM) reduced metabolism in the presence, but not the absence of NaCl. Azide (1 mM), cyanide (10 mM), and ascorbic acid (1 mM) dramatically inhibited metabolism. With glutathione (0.1 mM), a new metabolite was observed which was sensitive to (-glutamyl transpeptidase and hydrolyzed to ABZ with mild acid or base treatment (0.1 N HCl or 0.1 N NaOH for 10 min). In the presence of dGp, MPO or 0.3 mM NaOC l produced an adduct whose formation was prevented by the presence of either glutathione or vitamin C. ESI/MS/MS analysis demonstrated this adduct to be 1A. Thus, ABZ is a reducing co-substrate for MPO and a reductant for OCl-. MPO may be responsible for the activation of ABZ by peripheral white blood cells to form 1A.