Kashida T, Narasaki N, Tsujihara K, Naito K, Takeyama S
Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Int J Immunopharmacol. 1996 May;18(5):311-9. doi: 10.1016/0192-0561(96)00026-4.
Inhibitory effects on some immunological responses and MethA fibrosarcoma in the double grafted tumor system in mice were compared between 6-mercaptopurine (6-MP) and its novel water-soluble derivative, gamma-(9H-purine-6-yl)thiomethyl L-glutamate (6-MPG). The dose-dependent inhibitory effects by 6-MPG on the hemagglutinin response to SRBC, DTH reaction to MBSA, contact sensitivity to oxazolone, GVH response and growth of the primary tumor were 3-10 times weaker than those by 6-MP, probably reflecting the difference in their cytotoxicities antimetabolites. However, the two drugs were nearly equipotent in reproducing inhibition of the secondary tumor growth, which is a host-mediated immunological response to tumor antigen as shown by its dependency on the primary inoculation with 1 x 10(4) or more MethA cells and by the production of anti-tumor splenocytes in tumor-bearing animals (the Winn assay). Thus, 6-MPG may point to the direction of derivatization towards anti-tumor immunopotentiators with an improved therapeutic index.
在小鼠双移植肿瘤系统中，比较了6-巯基嘌呤（6-MP）及其新型水溶性衍生物γ-（9H-嘌呤-6-基）硫代甲基L-谷氨酸（6-MPG）对某些免疫反应和MethA纤维肉瘤的抑制作用。6-MPG对SRBC血凝素反应、对MBSA的迟发型超敏反应、对恶唑酮的接触敏感性、移植物抗宿主反应以及原发性肿瘤生长的剂量依赖性抑制作用比6-MP弱3至10倍，这可能反映了它们作为抗代谢物的细胞毒性差异。然而，这两种药物在抑制继发性肿瘤生长方面几乎具有同等效力，继发性肿瘤生长是宿主对肿瘤抗原的免疫反应，这表现为其依赖于接种1×10⁴个或更多的MethA细胞以及荷瘤动物中抗肿瘤脾细胞的产生（Winn试验）。因此，6-MPG可能为朝着具有改善治疗指数的抗肿瘤免疫增强剂的衍生化方向指明了道路。
