Evaluation of the genotoxicity of cis-bis(3-aminoflavone)dichloroplatinum(II) in comparison with cis-DDP

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2004-03, Vol.558 (1), p.93-110
• Main Authors: Kosmider, Beata, Wyszynska, Kalina, Janik-Spiechowicz, Ewa, Osiecka, Regina, Zyner, Elzbieta, Ochocki, Justyn, Ciesielska, Ewa, Wasowicz, Wojciech
• Format: Article
• Language: English
• Subjects: Ames assay; Biological and medical sciences; Chromosomal aberration assay; cis-bis(3-Aminoflavone)dichloroplatinum(II); cis-Diamminedichloroplatinum(II); Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Medical sciences; Micronucleus assay; Sister chromatid exchange assay; Toxicology
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2003.11.006

Short-term tests that detect genetic damage have provided information needed for evaluating carcinogenic risks of chemicals to man. The mutagenicity of cis-bis(3-aminoflavone)dichloroplatinum(II) ( cis-[Pt(AF) 2Cl 2]) in comparison with cis-diamminedichloroplatinum(II) ( cis-DDP) was evaluated in the standard plate-incorporation assay in four strains of Salmonella typhimurium: TA97a, TA98, TA100 and TA102, in experiments with and without metabolic activation. It was shown that cis-[Pt(AF) 2Cl 2] acts directly and is mutagenic for three strains of S. typhimurium: TA97a, TA98 and TA100. In comparison with cis-DDP this compound showed a weaker genotoxicity. Contrary to cis-DDP it has not shown toxic properties in the tester bacteria. The genotoxicity of both tested compounds was evaluated using chromosomal aberration, sister chromatid exchange and micronucleus assays, without and with metabolic activation, in human lymphocytes in vitro. The inhibitory effects of both compounds on mitotic activity, cell proliferation kinetics and nuclear division index were also compared. In all test systems applied, cis-[Pt(AF) 2Cl 2] was a less effective clastogen and a weaker inducer of both sister chromatid exchanges and micronuclei in comparison with cis-DDP, with and without metabolic activation. cis-[Pt(AF) 2Cl 2] has a direct mechanism of action and is less cytostatic and cytotoxic than the other compound. These results provide important data on the genotoxicity of cis-[Pt(AF) 2Cl 2] and indicate its beneficial properties as a potential anticancer drug, especially in comparison with cis-DDP.