Saccharomyces cerevisiae as Biosensor for Cyto- and Genotoxic Activity

  • Jost Ludwig
  • Marcel Schmitt
  • Hella Lichtenberg-Fraté

Abstract

Conventionally, toxicological bioassays are based on rodent models to evaluate the toxic effects of chemical compounds and to study the mechanism of action of toxicants. However, scientific developments are required to keep in line with regulatory frameworks, such as existing EU guidelines for assessment of manufactured chemicals (67/548/EEC, 93/67/EEC, and 83/571/EEC) and the EU regulatory framework for chemicals (REACH, EC1907/2006) concerning in part also existing chemicals. Scientific developments are thus directed towards rapid and reliable highthroughput assays to evaluate more accurately and more mechanistically the potential hazards of large numbers of chemicals. The yeast Saccharomyces cerevisiae is a promising model for such assays because it is amenable to genetic studies and because of the vast amount of genomics knowledge, resources, and manipulative tools associated with this unicellular fungus. The high degree of homology of essential cellular organization and metabolism shared by S. cerevisiae and higher eukaryotes has enabled the study of aspects of cellular toxicity and phenomena of relevance to human biology at the molecular level.

Keywords

Saccharomyces cerevisiae 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Afanassiev V, Sefton M, Anantachaiyong T, Barker G, Walmsley R, Wölfl S. (2000) Application of yeast cells transformed with GFP expression constructs containing the RAD54 or RNR2 promoter as a test for the genotoxic potential of chemical substances. Mutat Res 464:297–308Google Scholar
  2. Ambesi A, Miranda M, Petrov V V, Slayman C W (2000) Biogenesis and function of the yeast plasma-membrane H(+)-ATPase. J Exp Biol 203:155–160Google Scholar
  3. Ames B N, Lee F D, Durston W. E. (1973) An improved bacterial test system for the detection an classification of mutagens and carcinogens. Proc Nat. Acad Sci USA 70:782–786CrossRefGoogle Scholar
  4. Balzi E, Goffeau A. (1995) Yeast multidrug resistance: the PDR network. J Bioenerg Biomembr 27:71–76CrossRefGoogle Scholar
  5. Blackwell K J, Tobin J M, Avery S V, (1998) Manganese toxicity towards Saccharomyces cerevisiae: dependence on intracellular and extracellular magnesium concentrations. Appl Microbiol Biotech 49:751–757CrossRefGoogle Scholar
  6. Capieaux E, Vignais M L, Sentenac A, Goffeau A (1989) The yeast H+-ATPase gene is controlled by the promoter binding factor TUF. J Biol Chem 264:7437–46Google Scholar
  7. Castrillo J I, Oliver S G (2004) Yeast as touchstone in post-genomic research: strategies for integrative analysis in functional genomics. Biochem Mol Biol 37:93–106Google Scholar
  8. Cormack B P, Valdivia R H, Falkow S (1996) FACS-optimized mutants of the green fluorescent protein (GFP). Gene 173:33–38CrossRefGoogle Scholar
  9. Countryman P I, Heddle J A (1976) The production of micronuclei from chromosome aberrations in irradiated cultures of human lymphocytes. Mutat Res 41:321–332Google Scholar
  10. DaviesJ(1994) Inactivation of antibiotics and the dissemination of resistance genes. Science 264:375–382CrossRefGoogle Scholar
  11. Eide D J (2000) Metal ion transport in eukaryotic microorganisms: insights from Saccharomyces cerevisiae. Adv Microb Physiol 43:1–38CrossRefGoogle Scholar
  12. Eide D J (2001) Functional genomics and metal metabolism. Genome Biol 2: 1028.1–1028.3CrossRefGoogle Scholar
  13. Fernandes A R, Peixoto F P, Sa-Correia I (1998) Activation of the H+-ATPase in the plasma membrane of cells of Saccharomyces cerevisiae grown under mild copper stress. Arch Microbiol 171:6–12CrossRefGoogle Scholar
  14. Fish F, Lampert I, Halachmi A, Riesenfeld G, Herzberg M (1987) The SOS Chromotest kit: A rapid method for the detection of genotoxicity. Toxic Assess 2:135–147CrossRefGoogle Scholar
  15. Fortuniak A, Zadzinski R, Bilinski T, Bartosz G (1996) Glutathione depletion in the yeast Saccharomyces cerevisiae. Biochem Mol Biol Int 38:901–910Google Scholar
  16. Gardner T S, di Bernardo D, Lorenz D, Collins J J (2003) Inferring genetic networks and identifying compound mode of action via expression profiling. Science 301:102–105CrossRefGoogle Scholar
  17. Gasch A P, Huang M, Metzner S, Botstein D, Elledge S J, Brown P O (2001) Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Mol Biol Cell 12: 2987–3003Google Scholar
  18. Gasch A P, Spellman P T, Kao C M, Carmel-Harel O, Eisen M B, Storz G, Botstein D, Brown P O (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11: 4241–4257Google Scholar
  19. Gee P, Maron D M, Ames B N (1994) Detection and classification of mutagens: a set of base-specific Salmonella tester strains. Proc Natl Acad Sci USA 91: 11606–11610CrossRefGoogle Scholar
  20. Hampsey M (1991) A tester system for detection each of the six base-pair substitutions in Saccharomyces cerevisiae by selecting for an essential cysteine in iso-1-cytochrome c. Genetics 128:59–67Google Scholar
  21. Hasenbrink G, Sievernich A, Wildt L, Ludwig J, Lichtenberg-Fraté H (2006) Estrogenic effects of natural and synthetic compounds including tibolone assessed in Saccharomyces cerevisiae expressing the human estrogen α and β receptors. FASEB J 20:1552–1554CrossRefGoogle Scholar
  22. Huggett R L, Kimerle R A, Mehrle P M Jr, Bergmann H L (1992) Bio-markers: Biochemical, Physiological, and Histological Markers of Anthropogenic Stress. Lewis, Boca Raton, USAGoogle Scholar
  23. Kohn K W, Grimek-Ewig R A (1973) Alkaline elution analysis, a new approach to the study of DNA single-strand interruptions in cells. Cancer Res 33:1849–1853Google Scholar
  24. Kolaczkowska A, Goffeau A (1999) Regulation of pleiotropic drug resistance in yeast. Drug Resist Updat 2:403–414CrossRefGoogle Scholar
  25. Kolaczkowski M, Goffeau A (1997) Active efflux by multidrug transporters as one of the strategies to evade chemotherapy and novel practical implications of yeast pleiotropic drug resistance. Pharmacol Ther 76:219–242CrossRefGoogle Scholar
  26. Kolaczkowski M, Kolaczowska A, Luczynski J, Witek S, Goffeau A (1998) In vivo characterization of the drug resistance profile of the major ABC transporters and other components of the yeast pleiotropic drug resistance network. Microb Drug Resist 4:143–158CrossRefGoogle Scholar
  27. Kuo M H, Grayhack E (1994) A library of yeast genomic MCM1 binding sites contains genes involved in cell cycle control, cell wall and membrane structure, and metabolism. Mol Cell Biol 14:348–359Google Scholar
  28. Lichtenberg-Fraté H, Schmitt M, Gellert G, Ludwig J (2003). A yeast based method for the detection of cyto- and genotoxicity. Toxicol In Vitro 17:709–716CrossRefGoogle Scholar
  29. Mateus C, Avery S V (2000) Destabilized green fluorescent protein for monitoring dynamic changes in yeast gene expression with flow cytometry. Yeast 16: 1313–1323CrossRefGoogle Scholar
  30. McCarthy J F, Shugart L R (1990) Biomarkers of Environmental Contamination. Lewis, Boca Raton, USAGoogle Scholar
  31. Moskvina E, Imre E M, Ruis H (1999) Stress factors acting at the level of the plasma membrane induce transcription via the stress response element (STRE) of the yeast Saccharomyces cerevisiae. Mol Microbiol 32:1263–1272CrossRefGoogle Scholar
  32. Müller D, Natarajan A T, Obe G, Röhrborn G (1982) Sister-Chromatid-Exchange-Test. Georg Thieme Verlag, Stuttgart & New YorkGoogle Scholar
  33. Oda Y, Nakamura S I, Oki I, Kato T, Shinagawa H (1985) Evaluation of the new system (umu-test) for the detection of environmental mutagens and carcinogens. Mutat Res 147: 219–229Google Scholar
  34. Östling O, Johanson K J (1984) Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun 123:291–298CrossRefGoogle Scholar
  35. Otha T, Nakumara N, Moriya M, Shirasu T, Kada T (1984) The SOS-function-inducing activity of chemical mutagens in Escherichia coli. Mutat Res 131:101–109Google Scholar
  36. Quandt K, Frech K, Karas H, Wingender E, Werner T (1995) MatInd and MatIn-spector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res 23:4878–4884CrossRefGoogle Scholar
  37. Quillardet P, Huisman O, D’Ari R, Hofnung M (1982) SOS chromotest, a direct assay of induction of an SOS function in Escherichia coli K-12 to measure genotoxicity. Proc Natl Acad Sci USA 79:5971–5975CrossRefGoogle Scholar
  38. Rasio D, Murakumo Y, Robbins D, Roth T, Silve A, Negrini M, Schmidt C, Burczak J, Fishel R, Croce C M (1997) Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. Cancer Res 57:2378–2383Google Scholar
  39. Reifferscheid G, Heil J, Oda Y, Zahn R K (1991) A microplate version of the SOS/umu-test for rapid detection of genotoxins and genotoxic potentials of environmental samples. Mutat Res 253:215–222Google Scholar
  40. Resnick M A, Cox B S (2000) Yeast as an honorary mammal. Mutat Res 451:1–11Google Scholar
  41. Schmitt M, Gellert G, Kirberg B, Ludwig J, Lichtenberg-Fraté H (2002) Cy-Gene: Eine neue hefebasierte Methode zur Bestimmung des cytotoxischen und genotoxischen Potentials von Umweltgiften im Wasserbereich. Vom Wasser 99: 111–118Google Scholar
  42. Schmitt M, Gellert G, Lichtenberg-Fraté H (2005) The toxic potential of industrial effluents determined the Saccharomyces cerevisiae based assay. Water Res. 39:3211–3218CrossRefGoogle Scholar
  43. Schmitt M, Gellert G, Ludwig J, Lichtenberg-Fraté H (2005) Assessment of cyto- and genotoxic effects of a variety of chemicals using Saccharomyces cerevisiae. Acta Hydrochim Hydrobiol 33:56–63CrossRefGoogle Scholar
  44. Schmitt M, Gellert G, Ludwig J, Lichtenberg-Fraté H (2004) Phenotypic yeast growth analysis for chronic toxicity testing. Ecotoxicol Environ Safety 59:142–150CrossRefGoogle Scholar
  45. Schmitt M, Schwanewilm P, Ludwig J, Lichtenberg-Fraté H (2006) PMA1 as a housekeeping biomarker for the assessment of toxicant induced stress in Saccharomyces cerevisiae. Appl Environm Microbiol 72:1515–1522CrossRefGoogle Scholar
  46. Serrano R, Kielland-Brandt M, Fink G R (1986) Yeast plasma membrane H+-ATPase is essential for growth and has homology with (Na+-K+)-, K+-, and Ca2+-ATPases. Nature 319:689–693CrossRefGoogle Scholar
  47. Spratt B G (1994) Resistance to antibiotics mediated by target alterations. Science 264:388–393CrossRefGoogle Scholar
  48. Stohs S J, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18:321–336CrossRefGoogle Scholar
  49. Van Bambeke F, Balzi E, Tulkens P M (2000) Antibiotic efflux pumps. Biochem Pharmacol 60:457–70CrossRefGoogle Scholar
  50. Viegas CA, Supply P, Capieaux E, Van Dyck L, Goffeau A, Sa-Correia I (1994) Regulation of the expression of the H(+)-ATPase genes PMA1 and PMA2 during growth and effects of octanoic acid in Saccharomyces cerevisiae. Biochim Biophys Acta 1217:74–80Google Scholar
  51. Walmsley R M, Billinton N, Heyer W D (1997) Green fluorescent protein as a reporter for the DNA damage-induced gene RAD54 in Saccharomyces cerevisiae. Yeast 13: 1535–1545CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Jost Ludwig
    • 1
  • Marcel Schmitt
    • 2
  • Hella Lichtenberg-Fraté
    • 3
  1. 1.University of Bonn, IZMBKirschallee 1Germany
  2. 2.University of Bonn, IZMBKirschallee 1Germany
  3. 3.University of Bonn, IZMBKirschallee 1Germany

Personalised recommendations