Mutagenicity, cytotoxicity, and DNA binding of platinum(II)-chloroammines in Chinese hamster ovary cells.

Abstract The cytotoxicity and mutagenicity of the six platinum(II)chloroammines have been investigated in Chinese hamster ovary cells. For these compounds, the observed slopes of the mutation-induction curves (mutants/10 6 cells/µm) were: cis -Pt(NH 3 ) 2 Cl 2 (31.5), K[Pt(NH 3 )Cl 3 ] (2.78), [Pt(NH 3 ) 3 Cl]Cl (0.11), K 2 [PtCl 4 ] (0.12), trans -Pt(NH 3 ) 2 Cl 2 (0.013), and [Pt(NH 3 ) 4 ]Cl 2 (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. Results indicate that Chinese hamster ovary cells are useful in quantifying low mutagenic activity of chemicals such as platinum compounds. Studies with 195m Pt-labeled cis - and trans -Pt(NH 3 ) 2 Cl 2 showed that during treatment both compounds enter the cell and bind to the DNA with comparable efficiency. Hence, the relative mutagenicities of cis - and trans -Pt(NH 3 ) 2 Cl 2 are not a consequence of different initial levels of DNA binding.