An in vitro study comparing the cytotoxicity of three platinum complexes with regard to the effect of thiol depletion

Abstract

The cytotoxicity of three platinum complexes, cis-diamminedichloroplatinum(II) (cis-platin), cis-dichloro-trans-dihydroxy-cis-bis (isopropylamine) platinum(IV), (CHIP) and diammine (1, 1-cyclobutane-dicarboxylato) platinum(II) (carboplatin) on Chinese Hamster ovary (CHO) and mouse sarcoma RIF-1 cells cultured in vitro has been compared. The tumour cell line was much more sensitive to the cytotoxic action of the three agents compared to the CHO cell line. CHIP and carboplatin gave similar dose-response curves, both being much less toxic than cis-platin. The effect of thiol modification on platinum toxicity was also investigated. Substantial reduction in the intracellular non-protein sulphydryl content markedly enhanced the cytotoxicity of CHIP but had much less effect on carboplatin and cis-platin. Thiol depletion by diethylmaleate had a negligible effect on cis-platin toxicity.