A yeast-based method for the detection of cyto and genotoxicity

A miniaturized short-term in vivo genotoxicity screening assay based on genetically modified yeast ( Saccharomyces cerevisiae) cells was performed to explore the capacity of this eukaryotic organism to detect the presence of genotoxic compounds. An increased general sensitivity of yeast cells to tox...

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Veröffentlicht in:Toxicology in vitro 2003-10, Vol.17 (5), p.709-716
Hauptverfasser: Lichtenberg-Fraté, Hella, Schmitt, Marcel, Gellert, Georg, Ludwig, Jost
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container_issue 5
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container_title Toxicology in vitro
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creator Lichtenberg-Fraté, Hella
Schmitt, Marcel
Gellert, Georg
Ludwig, Jost
description A miniaturized short-term in vivo genotoxicity screening assay based on genetically modified yeast ( Saccharomyces cerevisiae) cells was performed to explore the capacity of this eukaryotic organism to detect the presence of genotoxic compounds. An increased general sensitivity of yeast cells to toxic compounds was obtained by using a strain being deleted in the prominent pleiotropic drug resistance mediating efflux transporters PDR5, SNQ2 and YOR1. In order to detect genotoxic effects, a yeast optimized version of the green fluorescent protein (GFP) was fused to the RAD54 promoter that is activated upon DNA damage. Various model substances including the oxygenated fuel additive methyl tertiary-butyl ether (MTBE) and the direct acting genotoxins methyl- N-nitro- N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4-NQO) were tested. All model substances were in parallel examined for chronic cytotoxicity. The results point out the sufficiency of both the sensitivity of the yeast cells to detect chronic cytotoxicity and the intensity of the fluorescence signal for the assessment of genotoxic effects. Thus, the test enables simultaneous detection of cytotoxic and genotoxic effects. By partial automation and implementation of the test in the microtitre scale this bioassay allows parallel sensitive pre-screening of numerous samples.
doi_str_mv 10.1016/S0887-2333(03)00129-2
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Biological and medical sciences
Cell Division - drug effects
Cell Division - physiology
Cytotoxicity
DNA Damage
DNA Helicases
DNA Repair Enzymes
Dose-Response Relationship, Drug
General aspects. Methods
Genotoxicity
GFP
Green Fluorescent Proteins
Luminescent Proteins - genetics
Luminescent Proteins - metabolism
Medical sciences
Mutagenicity Tests
Mutagens - toxicity
RAD54
Saccharomyces cerevisiae
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - physiology
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Short term in vitro test
Toxicology
Xenobiotics - toxicity
title A yeast-based method for the detection of cyto and genotoxicity
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