Protection of antiproliferative effect of cis-diamminedichloroplatinum (II) by sodium thiosulfate

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Abstract
Utilizing the phytohemagglutinin (PHA) stimulation assay of human peripheral blood mononuclear cells (PBM), the protective effect of sodium thiosulfate (STS) on the antiproliferative action of cis-diamminedichloroplatinum (II) (DDP) against human cells was investigated. DDP alone significantly inhibited the proliferation of PBM over the concentration range of 10-7 to 5x10-5 M. The antiproliferative effect of DDP was significantly blocked when STS was added to the stimulation culture at the time of exposure to DDP at molar STS/DDP ratios of more than 500. However, STS at molar ratios of less than 100 induced minimal protection. Then, STS was added at various times after DDP exposure with a molar STS/DDP ratio of 1000. The protection was effective within 10 min after exposure to DDP at a concentration of 5x10-5 M, whereas it was not effective beyond 30 min after the exposure. The results indicate that effective protection against DDP cytotoxicity in human cells can be achieved by the concurrent presence of STS with molar STS/DDP ratios of more than 500, but not when a molar STS/DDP ratio of less than 100 is used.