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Toxicity of CuO nanoparticles to yeast Saccharomyces cerevisiae BY4741 wild-type and its nine isogenic single-gene deletion mutants.
Chem Res Toxicol. 2013 Mar 18; 26(3):356-67.CR

Abstract

A suite of eight tentatively oxidative stress response-deficient Saccharomyces cerevisiae BY4741 single-gene mutants (sod1Δ, sod2Δ, yap1Δ, cta1Δ, ctt1Δ, gsh1Δ, glr1Δ, and ccs1Δ) and one copper-vulnerable mutant (cup2Δ) was used to elucidate weather the toxicity of CuO nanoparticles to S. cerevisiae is mediated by oxidative stress (OS). Specifically, sensitivity profiles of mutants' phenotypes and wild-type (wt) upon exposure to nano-CuO were compared. As controls, CuSO4 (solubility), bulk-CuO (size), H2O2, and menadione (OS) were used. Growth inhibition of wt and mutant strains was studied in rich YPD medium and cell viability in deionized water (DI). Dissolved Cu-ions were quantified by recombinant metal-sensing bacteria and chemical analysis. To wt strain nano-CuO was 32-fold more toxic than bulk-CuO: 24-h IC50 4.8 and 155 mg/L in DI and 643 and >20000 mg/L in YPD, respectively. In toxicant-free YPD medium, all mutants had practically similar growth patterns as wt. However, the mutant strains sod1Δ, sod2Δ, ccs1Δ, and yap1Δ showed up to 12-fold elevated sensitivity toward OS standard chemicals menadione and H2O2 but not to nano-CuO, indicating that CuO nanoparticles exerted toxicity to yeast cells via different mechanisms. The most vulnerable strain to all studied Cu compounds was the copper stress response-deficient strain cup2Δ (∼16-fold difference with wt), indicating that the toxic effect of CuO (nano)particles proceeds via dissolved Cu-ions. The dissolved copper solely explained the toxicity of nano-CuO in DI but not in YPD. Assumingly, in YPD nano-CuO acquired a coating of peptides/proteins and sorbed onto the yeast's outer surface, resulting in their increased solubility in the close vicinity of yeast cells and increased uptake of Cu-ions that was not registered by the assays used for the analysis of dissolved Cu-ions in the test medium. Lastly, as yeast retained its viability in DI even by 24th hour of incubation, the profiling of the acute basal toxicity of chemicals toward yeasts may be conducted in DI.

Authors+Show Affiliations

National Institute of Chemical Physics and Biophysics, Laboratory of Environmental Toxicology, Akadeemia tee 23, Tallinn, Estonia. kaja.kasemets@kbfi.eeNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23339633

Citation

Kasemets, Kaja, et al. "Toxicity of CuO Nanoparticles to Yeast Saccharomyces Cerevisiae BY4741 Wild-type and Its Nine Isogenic Single-gene Deletion Mutants." Chemical Research in Toxicology, vol. 26, no. 3, 2013, pp. 356-67.
Kasemets K, Suppi S, Künnis-Beres K, et al. Toxicity of CuO nanoparticles to yeast Saccharomyces cerevisiae BY4741 wild-type and its nine isogenic single-gene deletion mutants. Chem Res Toxicol. 2013;26(3):356-67.
Kasemets, K., Suppi, S., Künnis-Beres, K., & Kahru, A. (2013). Toxicity of CuO nanoparticles to yeast Saccharomyces cerevisiae BY4741 wild-type and its nine isogenic single-gene deletion mutants. Chemical Research in Toxicology, 26(3), 356-67. https://doi.org/10.1021/tx300467d
Kasemets K, et al. Toxicity of CuO Nanoparticles to Yeast Saccharomyces Cerevisiae BY4741 Wild-type and Its Nine Isogenic Single-gene Deletion Mutants. Chem Res Toxicol. 2013 Mar 18;26(3):356-67. PubMed PMID: 23339633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toxicity of CuO nanoparticles to yeast Saccharomyces cerevisiae BY4741 wild-type and its nine isogenic single-gene deletion mutants. AU - Kasemets,Kaja, AU - Suppi,Sandra, AU - Künnis-Beres,Kai, AU - Kahru,Anne, Y1 - 2013/02/14/ PY - 2013/1/24/entrez PY - 2013/1/24/pubmed PY - 2013/8/30/medline SP - 356 EP - 67 JF - Chemical research in toxicology JO - Chem Res Toxicol VL - 26 IS - 3 N2 - A suite of eight tentatively oxidative stress response-deficient Saccharomyces cerevisiae BY4741 single-gene mutants (sod1Δ, sod2Δ, yap1Δ, cta1Δ, ctt1Δ, gsh1Δ, glr1Δ, and ccs1Δ) and one copper-vulnerable mutant (cup2Δ) was used to elucidate weather the toxicity of CuO nanoparticles to S. cerevisiae is mediated by oxidative stress (OS). Specifically, sensitivity profiles of mutants' phenotypes and wild-type (wt) upon exposure to nano-CuO were compared. As controls, CuSO4 (solubility), bulk-CuO (size), H2O2, and menadione (OS) were used. Growth inhibition of wt and mutant strains was studied in rich YPD medium and cell viability in deionized water (DI). Dissolved Cu-ions were quantified by recombinant metal-sensing bacteria and chemical analysis. To wt strain nano-CuO was 32-fold more toxic than bulk-CuO: 24-h IC50 4.8 and 155 mg/L in DI and 643 and >20000 mg/L in YPD, respectively. In toxicant-free YPD medium, all mutants had practically similar growth patterns as wt. However, the mutant strains sod1Δ, sod2Δ, ccs1Δ, and yap1Δ showed up to 12-fold elevated sensitivity toward OS standard chemicals menadione and H2O2 but not to nano-CuO, indicating that CuO nanoparticles exerted toxicity to yeast cells via different mechanisms. The most vulnerable strain to all studied Cu compounds was the copper stress response-deficient strain cup2Δ (∼16-fold difference with wt), indicating that the toxic effect of CuO (nano)particles proceeds via dissolved Cu-ions. The dissolved copper solely explained the toxicity of nano-CuO in DI but not in YPD. Assumingly, in YPD nano-CuO acquired a coating of peptides/proteins and sorbed onto the yeast's outer surface, resulting in their increased solubility in the close vicinity of yeast cells and increased uptake of Cu-ions that was not registered by the assays used for the analysis of dissolved Cu-ions in the test medium. Lastly, as yeast retained its viability in DI even by 24th hour of incubation, the profiling of the acute basal toxicity of chemicals toward yeasts may be conducted in DI. SN - 1520-5010 UR - https://www.unboundmedicine.com/medline/citation/23339633/Toxicity_of_CuO_nanoparticles_to_yeast_Saccharomyces_cerevisiae_BY4741_wild_type_and_its_nine_isogenic_single_gene_deletion_mutants_ L2 - https://doi.org/10.1021/tx300467d DB - PRIME DP - Unbound Medicine ER -