Augmentation of tumor immunity by 6-mercaptopurine (6-MP) and its analogs in the double grafted tumor system in mice
| Autor: | Naoko Narasaki, Shigeyuki Takeyama, Kenji Tsujihara, Tatsuo Kashida, Kei Tsuzurahara, Atsuko Sakai |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Cellular immunity Antimetabolites Antineoplastic medicine.drug_class Fibrosarcoma T-Lymphocytes Pharmaceutical Science Spleen Immunostimulant Mice Immune system Antigen Adjuvants Immunologic medicine Animals Hypersensitivity Delayed Pharmacology Immunity Cellular Mice Inbred BALB C business.industry Mercaptopurine General Medicine medicine.disease Primary tumor Molecular biology medicine.anatomical_structure Immunology Drug Screening Assays Antitumor business CD8 Injections Intraperitoneal Neoplasm Transplantation |
| Zdroj: | Biologicalpharmaceutical bulletin. 18(11) |
| ISSN: | 0918-6158 |
| Popis: | We investigated the antitumor effect of 6-mercaptopurine (6-MP) and its analogs using the double grafted tumor technique. BALB/c mice were inoculated intradermally with MethA fibrosarcoma cells at the right inguinal region on day 0 (the primary tumor) and at the left on day 10 (the secondary tumor). Intraperitoneal or intra-lesional administration of 6-MP, 6-mercaptopurine riboside (6-MP-r) and 6-mercaptopurine riboside triacetate (6-MPRTA) from day 3 to 7 dose-dependently inhibited growth of the secondary tumor. Without the primary inoculation, 6-MP showed no effect on growth of the tumor inoculated on day 10, indicating that the antitumor effect of 6-MP could not be attributable to its direct antimetabolic or tumoricidal action only, and that the primary tumor inoculation is necessary for these compounds to inhibit growth of the challenging tumor. 6-MP did not inhibit the secondary MethA growth in the BALB/c (nu/nu) mouse. Both CD4+ and CD8+ T cells increased in the spleen of mice treated with 6-MP. Meanwhile, delayed-type hypersensitivity (DTH) reaction to the methylated bovine serum albumin (MBSA) antigen at the footpad was not augmented but inhibited by 6-MP, 6-MP-r and 6-MPRTA in both normal and tumor-bearing mice. Thus, the immunomodulatory activity of 6-MP could be observed in two opposite directions, augmentation of tumor immunity and inhibition of DTH to MBSA. This indicates that the immune mechanism and/or the type of effector cells induced in these two cell-mediated immune systems are different from each other. |
| Databáze: | OpenAIRE |
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