Evaluation of the cytotoxicity, genotoxicity and mutagenicity of diphenyl ditelluride in several biological models
| Autor: | Tiago Hoerbe Degrandi, Cícero Rafael Leão Garcia, Izabel Vianna Villela, Temenouga N. Guecheva, João Antonio Pêgas Henriques, Iuri Marques de Oliveira, Renato Moreira Rosa, Gabriel Silveira d'Almeida |
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| Rok vydání: | 2010 |
| Předmět: |
DNA damage
DNA repair Health Toxicology and Mutagenesis Saccharomyces cerevisiae Toxicology medicine.disease_cause Models Biological Thiobarbituric Acid Reactive Substances Cell Line chemistry.chemical_compound Cricetulus Salmonella Cricetinae Microsomes Benzene Derivatives Organometallic Compounds Genetics medicine Animals Point Mutation Micronuclei Chromosome-Defective Genetics (clinical) Cell Proliferation Microbial Viability Cell Death L-Lactate Dehydrogenase Mutagenicity Tests Diphenyl ditelluride Formamidopyrimidine DNA glycosylase Base excision repair Comet assay Oxidative Stress chemistry Biochemistry Biomarkers Oxidative stress Genotoxicity DNA Damage Mutagens |
| Zdroj: | Mutagenesis. 25:257-269 |
| ISSN: | 1464-3804 0267-8357 |
| Popis: | Diphenyl ditelluride (DPDT) is a potential prototype for the development of novel biologically active molecules. Thus, it is important to evaluate the toxic effects of this compound. In the present study, we evaluated the cytotoxic, genotoxic and mutagenic properties of DPDT in Chinese hamster fibroblast (V79) cells, in strains of the yeast Saccharomyces cerevisiae both proficient and deficient in several DNA repair pathways and in Salmonella typhimurium. DPDT induced frameshift mutations in both S.typhimurium and a haploid wild-type strain of S.cerevisiae. Mutants of S.cerevisiae defective in base excision repair and recombinational repair were more sensitive to DPDT. The results of a lactate dehydrogenase leakage assay suggest that DPDT is cytotoxic to V79 cells. At cytotoxic concentrations, this compound increased thiobarbituric reactive species levels and decreased the glutathione:GSSH ratio in yeast and V79 cells. DPDT generated single- and double-strand DNA breaks in V79 cells, both with and without metabolic activation, as revealed by alkaline and neutral comet assays. Moreover, an induction of oxidative DNA base damage was indicated by a modified comet assay using formamidopyrimidine DNA glycosylase and endonuclease III. Treatment with DPDT also induced micronucleus formation in V79 cells. Pre-incubation with N-acetylcysteine reduced DPDT's oxidative, genotoxic and mutagenic effects in yeast and V79 cells. Our results suggest that the toxic and mutagenic properties of DPDT may stem from its ability to disturb the redox balance of the cell, which leads to oxidative stress and the induction of DNA damage. |
| Databáze: | OpenAIRE |
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