Augmentation of Tumor Immunity by 6-Mercaptopurine (6-MP) and Its Analogs in the Double Grafted Tumor System in Mice
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概要
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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.
- 公益社団法人日本薬学会の論文
- 1995-11-15
著者
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酒井 敦子
田辺製薬(株) 医薬開発研究所
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辻原 健二
Research Laboratories, Tanabe Seiyaku Co., Ltd.
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竹山 茂之
Research Laboratories Tanabe Seiyaku Co. Ltd.
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黒葛原 啓
田辺製薬(株) 研究開発企画センター
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樫田 龍雄
Research Laboratories, Tanabe Seiyaku Co., Ltd.
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奈良崎 直子
Research Laboratories, Tanabe Seiyaku Co., Ltd.
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酒井 敦子
Research Laboratories, Tanabe Seiyaku Co., Ltd.
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黒葛原 啓
Research Laboratories, Tanabe Seiyaku Co., Ltd.
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樫田 龍雄
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,
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Tsujihara K
Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.
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樫田 龍雄
Lead Optimization Research Laboratory Tanabe Seiyaku Co. Ltd.
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辻原 健二
Research Laboratories Tanabe Seiyaku Co. Ltd.
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奈良崎 直子
Research Laboratories Tanabe Seiyaku Co. Ltd.
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