Hyslop R M, Jardine I
J Pharmacol Exp Ther. 1981 Sep;218(3):621-8.
Irreversible binding of a metabolite of 6-thiopurine to mammalian hepatic protein was demonstrated in vitro. Protein binding occurred with rat, hamster, rabbit, pig and human liver microsomes in the presence of NADPH and oxygen. The involvement of the cytochrome P-450 system in the activation of 6-thiopurine to the chemically reactive metabolite was supported by the effects of inhibitors of cytochrome P-450 mediated reactions and phenobarbital induction. The binding of the metabolite appeared to be through formation of a mixed disulfide between 6-thiopurine and protein thiols. In the presence of thiols such as glutathione, the irreversible protein binding of 6-thiopurine was inhibited. No significant binding of 6-thiopurine to other tissues was observed in vitro with rats.
在体外实验中证实了6-硫嘌呤的一种代谢产物与哺乳动物肝脏蛋白的不可逆结合。在NADPH和氧气存在的情况下，大鼠、仓鼠、兔子、猪和人类肝脏微粒体均出现了蛋白结合现象。细胞色素P-450介导反应的抑制剂和苯巴比妥诱导作用的效果支持了细胞色素P-450系统参与将6-硫嘌呤激活为化学反应性代谢产物的过程。该代谢产物的结合似乎是通过6-硫嘌呤与蛋白硫醇之间形成混合二硫键实现的。在存在谷胱甘肽等硫醇的情况下，6-硫嘌呤与蛋白的不可逆结合受到抑制。在体外实验中，未观察到大鼠体内6-硫嘌呤与其他组织的显著结合。
