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Biomedical subjects

Georg Gellert

Publications and source records attributed to Georg Gellert.

3 recordsLinked to original sources

The toxic potential of an industrial effluent determined with the Saccharomyces cerevisiae-based assay.

Increasing levels of environmental pollution and the continuous monitoring of water quality both request specific and sensitive methods for the detection of detrimental water contents. On a regulatory basis genotoxicity is assessed by the standard umu-test (ISO 13829) that responds to DNA damage induced by chemicals. The focus of this study was the examination of the toxic potential of samples taken from the wastewater treatment plant of a refinery factory to explore the applicability of the Saccharomyces cerevisiae (bakers yeast) test for the detection of bio-available genotoxic activity in complex matrices. The toxic potential of samples without pre-treatment and following centrifugation was determined with the eukaryotic Saccharomyces cerevisiae bioassay based on the transcriptional activation of the green fluorescent protein (gfp) fused to the DNA damage inducible RAD54 promoter and general growth inhibition. Primary effluent samples were taken as qualified sterile spot samples from the final effluent of the purification plant. The Saccharomyces cerevisiae assay yielded geno- and cytotoxic responses in all complex untreated and centrifuged samples with high reproducibility. The obtained results suggest that the yeast assay is suited as a screening tool to monitor genotoxic potential of wastewater.

Biological Assay↗

Phenotypic yeast growth analysis for chronic toxicity testing.

In Saccharomyces cerevisiae the pH-dependent growth inhibition of the heavy metals Cu(2+), Cr(6+), Zn(2+), Co(2+), and Cd(2+) was examined in comparison to that of organic solvents and pure compounds DMSO, MNNG, 4-NQO, MTBE, ethanol, and 2-AA. The assay was based on both S. cerevisiae wild-type and genetically modified cells deleted in the transporters Pdr5, Snq2, and Yor1 that facilitate pleiotropic drug resistance to explore the potential for short-term chronic aquatic toxicity tests. The strain deleted in the proteins that mediate the efflux of structurally diverse hydrophobic compounds exhibited high sensitive growth inhibition at low (0.04 mg/L 4-NQO) to moderate (5.5 mg/L DMSO) organic compound exposure. At pH 6.4 the EC(50)'s, for all tested heavy metals were significantly low, in contrast to acidic pH conditions, in which both strains were able to grow in the presence of high concentrations of the transition metals Cu(2+), Zn(2+), and Co(2+), with the pdr5 yor1 snq2 mutant being more tolerant. Cd(2+) exerted the highest toxicity, with an EC(50) of 0.49 mg/L. Obtained results were compared with data determined from growth-inhibition tests involving other unicellular species. The comparison provided evidence that yeast is a sensitive and practical model system for toxicological risk assessment.

Dose-Response Relationship, Drug↗

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 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.

Cell Division↗