MUTAGENICITY, CYTO-TOXICITY, AND DNA-BINDING OF PLATINUM(II)-CHLOROAMMINES IN CHINESE-HAMSTER OVARY CELLS

Abstract

The cytotoxicity and mutagenicity of 6 platinum (II) chloroammines were investigated in Chinese hamster ovary cells. For these compounds, the observed slopes of the mutation-induction curves (mutants/106 cells/.mu.M) were as follows: cis-Pt(NH3)2CI2 [cis-diamminedichloroplatinum (II)] (31.5), K[Pt(NH3)CI3] [potassium amminetrichloroplatinate] (2.78), [Pt(NH3)3Cl]Cl [triamminechloroplatinum chloride] (0.11), K2[PtCl4] [dipotassium tetrachloroplatinate] (0.12), trans-Pt(NH3)2Cl2 [trans-diamminedichloroplatinum (II)], (0.013) and [Pt(NH3)4]Cl2 [tetraammine platinum dichloride] (0.0). The relative cytotoxicity of these compounds follows the same order and is of similar magnitude. The observed relative mutagenicities of these compounds paralleled their reported potencies in the Ames assay and their relative antitumor activities. Chinese hamster ovary cells are useful in quantifying low mutagenic activity of chemicals such as Pt compounds. During treatment with 195mPt-labeled cis- and trans-Pt (NH3)Cl2, both compounds enter the cell and bind to the DNA with comparable efficiency. The relative mutagenicities of cis- and trans-Pt (NH3)2Cl2 are not a consequence of different initial levels of DNA binding.