Augmentation of tumor immunity by 6-MPG, a water-soluble derivative of 6-mercaptopurine, in mice.
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.
Kashida
T
T
Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Narasaki
N
N
Tsujihara
K
K
Naito
K
K
Takeyama
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D005354:Fibrosarcoma / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary; D006384:Hemagglutination / Q000187:drug effects; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary; D012995:Solubility; D013154:Spleen / Q000637:transplantation
D000276:Adjuvants, Immunologic; D015122:Mercaptopurine