Evaluation of the cytotoxicity, genotoxicity and mutagenicity of diphenyl ditelluride in several biological models.
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.
Degrandi
Tiago Hoerbe
TH
Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
de Oliveira
Iuri Marques
IM
d'Almeida
Gabriel Silveira
GS
Garcia
Cícero Rafael Leão
CR
Villela
Izabel Vianna
IV
Guecheva
Temenouga Nikolova
TN
Rosa
Renato Moreira
RM
Henriques
João Antonio Pêgas
JA
D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009942:Organometallic Compounds / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017354:Point Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects; D012475:Salmonella / Q000166:cytology / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001555:Benzene Derivatives; D015415:Biomarkers; D009153:Mutagens; D009942:Organometallic Compounds; D017392:Thiobarbituric Acid Reactive Substances; C434247:diphenylditelluride; D007770:L-Lactate Dehydrogenase