Evaluation of the cytotoxicity, genotoxicity and mutagenicity of diphenyl ditelluride in several biological models

• Published in: Mutagenesis Vol. 25; no. 3; pp. 257 - 269
• Main Authors: Degrandi, Tiago Hoerbe, de Oliveira, Iuri Marques, d'Almeida, Gabriel Silveira, Garcia, Cícero Rafael Leão, Villela, Izabel Vianna, Guecheva, Temenouga Nikolova, Rosa, Renato Moreira, Henriques, João Antonio Pêgas
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2010
• Subjects: Animals; Benzene Derivatives - chemistry; Benzene Derivatives - toxicity; Biological and medical sciences; Biomarkers - metabolism; Cell Death - drug effects; Cell Line; Cell Proliferation - drug effects; Cricetinae; Cricetulus; DNA Damage; Fundamental and applied biological sciences. Psychology; L-Lactate Dehydrogenase - metabolism; Microbial Viability - drug effects; Micronuclei, Chromosome-Defective - drug effects; Microsomes - drug effects; Microsomes - metabolism; Models, Biological; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Mutagenicity Tests; Mutagens - chemistry; Mutagens - toxicity; Organometallic Compounds - chemistry; Organometallic Compounds - toxicity; Oxidative Stress - drug effects; Point Mutation - genetics; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - drug effects; Salmonella - cytology; Salmonella - drug effects; Thiobarbituric Acid Reactive Substances - metabolism; Cytotoxicity; Models; Mutagenesis; Toxicity; Genotoxicity
• ISSN: 0267-8357; 1464-3804
• DOI: 10.1093/mutage/geq002

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.