The effects of dichloro-trans-dihydroxy-bis-isopropyl-amine-platinum IV on the primary cell-mediated cytotoxic response.

The effects of diamino-dichloro-cis-platinum II (DDP) and dichloro-trans-bis-isopropyl-amine-platinum IV (DDIP or CHIP) on the primary cell-mediated cytotoxic (CMC) response developed in a mixed lymphocyte tumor cell culture (MLTC) were investigated. DDP as well as CHIP added on day 0 augmented the CMC response when spleen cells from C57Bl/6 mice were cultured for 4 days with supraoptimal numbers of irradiated (4000 rads) allogeneic P815 mastocytoma cells. A similar effect was observed when mice were treated with either of the two platinum compounds 1 or 5 days prior to spleen removal and sensitization of the spleen cells in a MLTC. Augmentation was not observed at optimal or suboptimal R:S. When spleen cells were preincubated with CHIP, only inhibitory effects on the CMC response could be demonstrated. Decreasing Cl- -ion concentrations in the preincubation medium increased the inhibitory effect of CHIP. After CHIP administration to spleen donor mice, the development of antigen specific suppressor cells was inhibited only at doses higher than those required to inhibit the development of nonspecific suppressor cells. Spleen responder cells from CHIP-treated donors exhibited a lower sensitivity to both antigen-specific and nonspecific suppressor cells than spleen responder cells from untreated control donors.