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Mutagenicity, Cytotoxicity, and DNA Binding of Platinum(II)-chloroammines in Chinese Hamster Ovary Cells¹

University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences [N. P. J.], and Biology [R. O. R., J. P. O., A. W. H.] and Health and Safety Research [J. D. H.] Divisions, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830

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/10⁶ cells/µM) were: cis-Pt(NH₃)₂Cl₂ (31.5), K[Pt(NH₃)Cl₃] (2.78), [Pt(NH₃)₃Cl]Cl (0.11), K₂[PtCl₄] (0.12), trans-Pt(NH₃)₂Cl₂ (0.013), and [Pt(NH₃)₄]Cl₂ (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 ^195mPt-labeled cis- and trans-Pt(NH₃)₂Cl₂ 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(NH₃)₂Cl₂ are not a consequence of different initial levels of DNA binding.

¹ Research sponsored jointly by the Environmental Protection Agency (IAG-D5-E81) and the Office of Health and Environmental Research, United States Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation.

² Supported by an American Cancer Society Postdoctoral Fellowship and Carcinogenesis Training Grant CA 05296 from the National Cancer Institute. Present address: Laboratoire de Pharmacologie et de Toxicology Fondamentales, 205 Route de Narbonne, 31078 Toulouse Cedex, France.

³ To whom requests for reprints should be addressed.

Received 10/17/79. Accepted 1/23/80.

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