Effect of mannitol and plasma on the cytotoxicity of cisplatin

A soft agar cell culture for human granulocyte precursor cells (CFU-c) was used to assess the cytotoxic effect of cisplatin before and after preincubating the drug with either mannitol and/or fresh human plasma. Consistent growth inhibition of CFU-c was found with survival of 87, 64 and 34% at cisplatin concentrations of 10(-7) M, 10(-6) M and 10(-5) M respectively. Dose-related survival was not changed by preincubating cisplatin with mannitol in molar ratios of 1:100 and 1:1000 for 4 and 24 hr. Preincubating 10(-5) M cisplatin with human plasma increased CFU-c survival corresponding to a loss of activity of 92 and 98% after 4- and 24-hr preincubations respectively. No significant difference in survival of CFU-c was noted whether bone marrow cells were exposed to cisplatin in human plasma or in the ultrafiltrate of human plasma. Mannitol did not change the decrease in cisplatin activity due to plasma protein binding. These data indicate that the cytotoxic effect of cisplatin can be reduced by exposure to human plasma but not to mannitol.