AUGMENTATION OF TUMOR-IMMUNITY BY 6-MERCAPTOPURINE (6-MP) AND ITS ANALOGS IN THE DOUBLE GRAFTED TUMOR SYSTEM IN MICE

We investigated the antitumor effect of 6-mercaptopurine (6-MP) and it s analogs using the double grafted tumor technique, BALB/c mice were i noculated intradermally with MethA fibrosarcoma cells at the right ing uinal region on day 0 (the primary tumor) and at the left on day 10 (t he secondary tumor), Intraperitoneal or intra-lesional administration of 6-MP, 6-mercaptopurine riboside (6-MP-r) and 6-mercaptopurine ribos ide triacetate (6-MPRTA) from day 3 to 7 dose-dependently inhibited gr owth of the secondary tumor, Without the primary inoculation, 6-MP sho wed no effect on grow th of the tumor inoculated on day 10, indicating that the antitumor effect of 6-MP could not be attributable to its di rect antimetabolic or tumoricidal action only, and that the primary tu mor 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 hype rsensitivity (DTH) reaction to the methylated bovine serum albumin (MB SA) 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 immu nomodulatory activity of 6-MP could be observed in two opposite direct ions, augmentation of tumor immunity and inhibition of DTH to MBSA. Th is indicates that the immune mechanism and/or the type of effector cel ls induced in these two cell-mediated immune systems are different fro m each other.