Hyslop R M, Jardine I
J Pharmacol Exp Ther. 1981 Sep;218(3):629-35.
After injection of 6-thio[8-14C]purine i.p. in rats or rabbits radioactivity was shown to be irreversibly bound to protein of all tissues examined except brain. The binding increased with time after a single injection and increased nonlinearly in response to dose. Binding per milligram of protein was most extensive in intestine, spleen and liver. Binding in liver was primarily to microsomal protein with no binding detected in microsomal nucleic acid. Hepatic microsomal protein binding increased in rats fed a protein-free diet to deplete the hepato-cellular glutathione concentration. Binding to hepatic microsomal protein was decreased by pretreatment with phenobarbital or piperonyl butoxide, but not significantly with allopurinol. 6-Thiopurine at therapeutic doses had no apparent negative effects on either hepatocellular glutathione levels or hepatic microsomal aminopyrine N-demethylase activity during this time period. These observations may be significant regarding reported toxic side effects associated with 6-thiopurine.
给大鼠或家兔腹腔注射6-硫代[8-¹⁴C]嘌呤后，放射性被证明不可逆地结合到除脑以外的所有被检查组织的蛋白质上。单次注射后，结合随时间增加，且对剂量呈非线性增加。每毫克蛋白质的结合在肠道、脾脏和肝脏中最为广泛。肝脏中的结合主要是与微粒体蛋白结合，在微粒体核酸中未检测到结合。喂食无蛋白饮食以耗尽肝细胞谷胱甘肽浓度的大鼠，其肝脏微粒体蛋白结合增加。用苯巴比妥或胡椒基丁醚预处理可降低与肝脏微粒体蛋白的结合，但用别嘌呤醇预处理则无显著降低。在此时间段内，治疗剂量的6-硫嘌呤对肝细胞谷胱甘肽水平或肝脏微粒体氨基比林N-脱甲基酶活性均无明显负面影响。这些观察结果对于报道的与6-硫嘌呤相关的毒性副作用可能具有重要意义。
