Applied Microbiology and Biotechnology

, Volume 102, Issue 6, pp 2493–2507 | Cite as

Yeast-based genotoxicity tests for assessing DNA alterations and DNA stress responses: a 40-year overview

  • Toshihiko Eki


By damaging DNA molecules, genotoxicants cause genetic mutations and also increase human susceptibility to cancers and genetic diseases. Over the past four decades, several assays have been developed in the budding yeast Saccharomyces cerevisiae to screen potential genotoxic substances and provide alternatives to animal-based genotoxicity tests. These yeast-based genotoxicity tests are either DNA alteration-based or DNA stress-response reporter-based. The former, which came first, were developed from the genetic studies conducted on various types of DNA alterations in yeast cells. Despite their limited throughput capabilities, some of these tests have been used as short-term genotoxicity tests in addition to bacteria- or mammalian cell-based tests. In contrast, the latter tests are based on the emergent transcriptional induction of DNA repair-related genes via activation of the DNA damage checkpoint kinase cascade triggered by DNA damage. Some of these reporter assays have been linked to DNA damage-responsive promoters to assess chemical carcinogenicity and ecotoxicity in environmental samples. Yeast-mediated genotoxicity tests are being continuously improved by increasing the permeability of yeast cell walls, by the ectopic expression of mammalian cytochrome P450 systems, by the use of DNA repair-deficient host strains, and by integrating them into high-throughput formats or microfluidic devices. Notably, yeast-based reporter assays linked with the newer toxicogenomic approaches are becoming powerful short-term genotoxicity tests for large numbers of compounds. These tests can also be used to detect polluted environmental samples, and as effective screening tools during anticancer drug development.


Saccharomyces cerevisiae Genotoxicity test DNA alteration Mutagen Anticancer drug Reporter assay 



I thank Dr. Yuu Hirose and all members of my laboratory for their support and helpful discussions. I thank Drs. Sandra Cheesman and Shelley Robison from Edanz Group ( for editing drafts of this manuscript.


This work was supported in part by a Grant-in-Aid for Scientific Research in Innovative Areas “Plasma Medical Innovation” (24108005) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (to T.E.).

Compliance with ethical standards

Conflict of interest

The author declares that there is no conflict of interest.

Ethical statement

This article does not describe any studies with human participants or with animals that were performed by the author.


  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 464:297–308PubMedCrossRefGoogle Scholar
  2. Albertini S, Zimmermann FK (1991) The detection of chemically induced chromosomal malsegregation in Saccharomyces cerevisiae D61.M: a literature survey (1984-1990). Mutat Res 258:237–258PubMedCrossRefGoogle Scholar
  3. Ames BN, Durston WE, Yamasaki E, Lee FD (1973) Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A 70:2281–2285PubMedPubMedCentralCrossRefGoogle Scholar
  4. Azevedo F, Marques F, Fokt H, Oliveira R, Johansson B (2011) Measuring oxidative DNA damage and DNA repair using the yeast comet assay. Yeast 28:55–61. PubMedCrossRefGoogle Scholar
  5. Baronian KH (2004) The use of yeast and moulds as sensing elements in biosensors. Biosens Bioelectron 19:953–962. PubMedCrossRefGoogle Scholar
  6. Bartoš T, Letzsch S, Škarek M, Flegrová Z, Čupr P, Holoubek I (2006) GFP assay as a sensitive eukaryotic screening model to detect toxic and genotoxic activity of azaarenes. Environ Toxicol 21:343–348. PubMedCrossRefGoogle Scholar
  7. Beljanski V, Marzilli LG, Doetsch PW (2004) DNA damage-processing pathways involved in the eukaryotic cellular response to anticancer DNA cross-linking drugs. Mol Pharmacol 65:1496–1506. PubMedCrossRefGoogle Scholar
  8. Benton MG, Somasundaram S, Glasner JD, Palecek SP (2006) Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation. BMC Genomics 7:305. PubMedPubMedCentralCrossRefGoogle Scholar
  9. Benton MG, Glasser NR, Palecek SP (2007) The utilization of a Saccharomyces cerevisiae HUG1P-GFP promoter-reporter construct for the selective detection of DNA damage. Mutat Res 633:21–34. PubMedCrossRefGoogle Scholar
  10. Benton MG, Glasser NR, Palecek SP (2008) Deletion of MAG1 and MRE11 enhances the sensitivity of the Saccharomyces cerevisiae HUG1P-GFP promoter-reporter construct to genotoxicity. Biosens Bioelectron 24:736–741. PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bianchi L, Zannoli A, Pizzala R, Stivala LA, Chiesara E (1994) Genotoxicity assay of five pesticides and their mixtures in Saccharomyces cerevisiae D7. Mutat Res 321:203–211PubMedCrossRefGoogle Scholar
  12. Billet S, Paget V, Garçon G, Heutte N, André V, Shirali P, Sichel F (2010) Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the functional analysis of separated alleles in yeast, in human lung cells. Arch Toxicol 84:99–107. PubMedCrossRefGoogle Scholar
  13. Billinton N, Barker MG, Michel CE, Knight AW, Heyer WD, Goddard NJ, Fielden PR, Walmsley RM (1998) Development of a green fluorescent protein reporter for a yeast genotoxicity biosensor. Biosens Bioelectron 13:831–838PubMedCrossRefGoogle Scholar
  14. Black SM, Ellard S, Meehan RR, Parry JM, Adesnik M, Beggs JD, Wolf CR (1989) The expression of cytochrome P450IIB1 in Saccharomyces cerevisiae results in an increased mutation frequency when exposed to cyclophosphamide. Carcinogenesis 10:2139–2143PubMedCrossRefGoogle Scholar
  15. Black SM, Ellard S, Parry JM, Wolf CR (1992) Increased sterigmatocystin-induced mutation frequency in Saccharomyces cerevisiae expressing cytochrome P450 CYP2B1. Biochem Pharmacol 43:374–376PubMedCrossRefGoogle Scholar
  16. Boronat S, Piña B (2006) Development of RNR3- and RAD54-GUS reporters for testing genotoxicity in Saccharomyces cerevisiae. Anal Bioanal Chem 386:1625–1632. PubMedCrossRefGoogle Scholar
  17. Božina N, Bradamante V, Lovrić M (2009) Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 60:217–242. PubMedCrossRefGoogle Scholar
  18. Brennan RJ, Swoboda BE, Schiestl RH (1994) Oxidative mutagens induce intrachromosomal recombination in yeast. Mutat Res 308:159–167PubMedCrossRefGoogle Scholar
  19. Bronzetti G, Zeiger E, Frezza D (1978) Genetic activity of trichloroethylene in yeast. J Environ Pathol Toxicol 1:411–418PubMedGoogle Scholar
  20. Brusick DJ, Mayer VW (1973) New developments in mutagenicity screening techniques with yeast. Environ Health Perspect 6:83–96PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bui VN, Nguyen TT, Bettarel Y, Nguyen TH, Pham TL, Hoang TY, Nguyen VT, Nghiem NM, Wölfl S (2015) Genotoxicity of chemical compounds identification and assessment by yeast cells transformed with GFP reporter constructs regulated by the PLM2 or DIN7 promoter. Int J Toxicol 34:31–43. PubMedCrossRefGoogle Scholar
  22. Bui VN, Nguyen TT, Mai CT, Bettarel Y, Hoang TY, Trinh TT, Truong NH, Chu HH, Nguyen VT, Nguyen HD, Wölfl S (2016) Procarcinogens—determination and evaluation by yeast-based biosensor transformed with plasmids incorporating RAD54 reporter construct and cytochrome P450 genes. PLoS One 11:e0168721. PubMedPubMedCentralCrossRefGoogle Scholar
  23. Buschini A, Cassoni F, Anceschi E, Pasini L, Poli P, Rossi C (2001) Urban airborne particulate: genotoxicity evaluation of different size fractions by mutagenesis tests on microorganisms and comet assay. Chemosphere 44:1723–1736PubMedCrossRefGoogle Scholar
  24. Caba E, Dickinson DA, Warnes GR, Aubrecht J (2005) Differentiating mechanisms of toxicity using global gene expression analysis in Saccharomyces cerevisiae. Mutat Res 575:34–46. PubMedCrossRefGoogle Scholar
  25. Cachot J, Couteau J, Frébourg T, Leboulenger F, Flaman JM (2004) Functional analysis of chemically-induced mutations at the flounder TP53 locus, the FACIM assay. Mutat Res 552:51–60. PubMedCrossRefGoogle Scholar
  26. Cahill PA, Knight AW, Billinton N, Barker MG, Walsh L, Keenan PO, Williams CV, Tweats DJ, Walmsley RM (2004) The GreenScreen genotoxicity assay: a screening validation programme. Mutagenesis 19:105–119PubMedCrossRefGoogle Scholar
  27. Chang M, Bellaoui M, Boone C, Brown GW (2002) A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage. Proc Natl Acad Sci U S A 99:16934–16939. PubMedPubMedCentralCrossRefGoogle Scholar
  28. Cormack BP, Bertram G, Egerton M, Gow NA, Falkow S, Brown AJ (1997) Yeast-enhanced green fluorescent protein (yEGFP): a reporter of gene expression in Candida albicans. Microbiology 143(Pt 2):303–311. PubMedCrossRefGoogle Scholar
  29. Daniel M, Sharpe A, Driver J, Knight AW, Keenan PO, Walmsley RM, Robinson A, Zhang T, Rawson D (2004) Results of a technology demonstration project to compare rapid aquatic toxicity screening tests in the analysis of industrial effluents. J Environ Monit 6:855–865. PubMedCrossRefGoogle Scholar
  30. Del Carratore MR, Mezzatesta C, Hidestrand M, Neve P, Amato G, Gervasi PG (2000) Cloning and expression of rat CYP2E1 in Saccharomyces cerevisiae: detection of genotoxicity of N-alkylformamides. Environ Mol Mutagen 36:97–104PubMedCrossRefGoogle Scholar
  31. Dimitrov M, Venkov P, Pesheva M (2011) The positive response of Ty1 retrotransposition test to carcinogens is due to increased levels of reactive oxygen species generated by the genotoxins. Arch Toxicol 85:67–74. PubMedCrossRefGoogle Scholar
  32. el-Abidin Salam AZ, Hussein EH, el-Itriby HA, Anwar WA, Mansour SA (1993) The mutagenicity of Gramoxone (paraquat) on different eukaryotic systems. Mutat Res 319:89–101PubMedCrossRefGoogle Scholar
  33. Elledge SJ, Zhou Z, Allen JB, Navas TA (1993) DNA damage and cell cycle regulation of ribonucleotide reductase. BioEssays 15:333–339PubMedCrossRefGoogle Scholar
  34. Fasullo M, Freedland J, St John N, Cera C, Egner P, Hartog M, Ding X (2017) An in vitro system for measuring genotoxicity mediated by human CYP3A4 in Saccharomyces cerevisiae. Environ Mol Mutagen 58:217–227. PubMedCrossRefGoogle Scholar
  35. Ferguson LR, Turner PM (1988a) Mitotic crossing-over by anticancer drugs in Saccharomyces cerevisiae strain D5. Mutat Res 204:239–249PubMedCrossRefGoogle Scholar
  36. Ferguson LR, Turner PM (1988b) ‘Petite’ mutagenesis by anticancer drugs in Saccharomyces cerevisiae. Eur J Cancer Clin Oncol 24:591–596PubMedCrossRefGoogle Scholar
  37. Frassinetti S, Barberio C, Caltavuturo L, Fava F, Di Gioia D (2011) Genotoxicity of 4-nonylphenol and nonylphenol ethoxylate mixtures by the use of Saccharomyces cerevisiae D7 mutation assay and use of this text to evaluate the efficiency of biodegradation treatments. Ecotoxicol Environ Saf 74:253–258. PubMedCrossRefGoogle Scholar
  38. Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T (2005) DNA repair and mutagenesis, 2nd edn. American Society for Microbiology Press, Washington, DCGoogle Scholar
  39. Fry RC, DeMott MS, Cosgrove JP, Begley TJ, Samson LD, Dedon PC (2006) The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA. BMC Genomics 7:313. PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fu Y, Pastushok L, Xiao W (2008) DNA damage-induced gene expression in Saccharomyces cerevisiae. FEMS Microbiol Rev 32:908–926. PubMedCrossRefGoogle Scholar
  41. García-Alonso J, Greenway GM, Hardege JD, Haswell SJ (2009) A prototype microfluidic chip using fluorescent yeast for detection of toxic compounds. Biosens Bioelectron 24:1508–1511. PubMedCrossRefGoogle Scholar
  42. García-Alonso J, Fakhrullin RF, Paunov VN (2010) Rapid and direct magnetization of GFP-reporter yeast for micro-screening systems. Biosens Bioelectron 25:1816–1819. PubMedCrossRefGoogle Scholar
  43. García-Alonso J, Fakhrullin RF, Paunov VN, Shen Z, Hardege JD, Pamme N, Haswell SJ, Greenway GM (2011) Microscreening toxicity system based on living magnetic yeast and gradient chips. Anal Bioanal Chem 400:1009–1013. PubMedCrossRefGoogle Scholar
  44. Giaever G, Flaherty P, Kumm J, Proctor M, Nislow C, Jaramillo DF, Chu AM, Jordan MI, Arkin AP, Davis RW (2004) Chemogenomic profiling: identifying the functional interactions of small molecules in yeast. Proc Natl Acad Sci U S A 101:793–798. PubMedPubMedCentralCrossRefGoogle Scholar
  45. Giorgetti L, Talouizte H, Merzouki M, Caltavuturo L, Geri C, Frassinetti S (2011) Genotoxicity evaluation of effluents from textile industries of the region Fez-Boulmane, Morocco: a case study. Ecotoxicol Environ Saf 74:2275–2283. PubMedCrossRefGoogle Scholar
  46. Guo Y, Breeden LL, Zarbl H, Preston BD, Eaton DL (2005) Expression of a human cytochrome P450 in yeast permits analysis of pathways for response to and repair of aflatoxin-induced DNA damage. Mol Cell Biol 25:5823–5833. PubMedPubMedCentralCrossRefGoogle Scholar
  47. Hannan MA, Nasim A (1978) Genetic activity of bleomycin: differential effects on mitotic recombination and mutations in yeast. Mutat Res 53:309–316PubMedCrossRefGoogle Scholar
  48. Hastwell PW, Chai LL, Roberts KJ, Webster TW, Harvey JS, Rees RW, Walmsley RM (2006) High-speciticity and high-sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. Mutat Res 607:160–175. PubMedCrossRefGoogle Scholar
  49. Hendriks G, Atallah M, Morolli B, Calléja F, Ras-Verloop N, Huijskens I, Raamsman M, van de Water B, Vrieling H (2012) The ToxTracker assay: novel GFP reporter systems that provide mechanistic insight into the genotoxic properties of chemicals. Toxicol Sci 125:285–298. PubMedCrossRefGoogle Scholar
  50. Hilscherová K, Dušek L, Šidlová T, Jálová V, Čupr P, Giesy JP, Nehyba S, Jarkovský J, Klánová J, Holoubek I (2010) Seasonally and regionally determined indication potential of bioassays in contaminated river sediments. Environ Toxicol Chem 29:522–534. PubMedCrossRefGoogle Scholar
  51. Hontzeas N, Hafer K, Schiestl RH (2007) Development of a microtiter plate version of the yeast DEL assay amenable to high-throughput toxicity screening of chemical libraries. Mutat Res 634:228–234. PubMedCrossRefGoogle Scholar
  52. Ichikawa K, Eki T (2006) A novel yeast-based reporter assay system for the sensitive detection of genotoxic agents mediated by a DNA damage-inducible LexA-GAL4 protein. J Biochem 139:105–112. PubMedCrossRefGoogle Scholar
  53. Inga A, Iannone R, Monti P, Molina F, Bolognesi M, Abbondandolo A, Iggo R, Fronza G (1997) Determining mutational fingerprints at the human p53 locus with a yeast functional assay: a new tool for molecular epidemiology. Oncogene 14:1307–1313. PubMedCrossRefGoogle Scholar
  54. Jarque S, Bittner M, Blaha L, Hilscherova K (2016) Yeast biosensors for detection of environmental pollutants: current state and limitations. Trends Biotechnol 34:408–419. PubMedCrossRefGoogle Scholar
  55. Jia X, Xiao W (2003) Compromised DNA repair enhances sensitivity of the yeast RNR3-lacZ genotoxicity testing system. Toxicol Sci 75:82–88PubMedCrossRefGoogle Scholar
  56. Jia X, Zhu Y, Xiao W (2002) A stable and sensitive genotoxic testing system based on DNA damage induced gene expression in Saccharomyces cerevisiae. Mutat Res 519:83–92PubMedCrossRefGoogle Scholar
  57. Keenan PO, Knight AW, Billinton N, Cahill PA, Dalrymple IM, Hawkyard CJ, Stratton-Campbell D, Walmsley RM (2007) Clear and present danger? The use of a yeast biosensor to monitor changes in the toxicity of industrial effluents subjected to oxidative colour removal treatments. J Environ Monit 9:1394–1401. PubMedCrossRefGoogle Scholar
  58. Kirpnick Z, Homiski M, Rubitski E, Repnevskaya M, Howlett N, Aubrecht J, Schiestl RH (2005) Yeast DEL assay detects clastogens. Mutat Res 582:116–134. PubMedCrossRefGoogle Scholar
  59. Klis FM, Mol P, Hellingwerf K, Brul S (2002) Dynamics of cell wall structure in Saccharomyces cerevisiae. FEMS Microbiol Rev 26:239–256PubMedCrossRefGoogle Scholar
  60. Knight AW, Keenan PO, Goddard NJ, Fielden PR, Walmsley RM (2004) A yeast-based cytotoxicity and genotoxicity assay for environmental monitoring using novel portable instrumentation. J Environ Monit 6:71–79. PubMedCrossRefGoogle Scholar
  61. Knight AW, Billinton N, Cahill PA, Scott A, Harvey JS, Roberts KJ, Tweats DJ, Keenan PO, Walmsley RM (2007) An analysis of results from 305 compounds tested with the yeast RAD54-GFP genotoxicity assay (GreenScreen GC)-including relative predictivity of regulatory tests and rodent carcinogenesis and performance with autofluorescent and coloured compounds. Mutagenesis 22:409–416. PubMedCrossRefGoogle Scholar
  62. Kreuzer KN (2013) DNA damage responses in prokaryotes: regulating gene expression, modulating growth patterns, and manipulating replication forks. Cold Spring Harb Perspect Biol 5:a012674. PubMedPubMedCentralCrossRefGoogle Scholar
  63. Ku WW, Aubrecht J, Mauthe RJ, Schiestl RH, Fornace AJ Jr (2007) Genetic toxicity assessment: employing the best science for human safety evaluation Part VII: Why not start with a single test: a transformational alternative to genotoxicity hazard and risk assessment. Toxicol Sci 99:20–25. PubMedCrossRefGoogle Scholar
  64. Lah B, Gorjanc G, Nekrep FV, Marinsek-Logar R (2004) Comet assay assessment of wastewater genotoxicity using yeast cells. Bull Environ Contam Toxicol 72:607–616. PubMedCrossRefGoogle Scholar
  65. Lan J, Gou N, Gao C, He M, Gu AZ (2014) Comparative and mechanistic genotoxicity assessment of nanomaterials via a quantitative toxicogenomics approach across multiple species. Environ Sci Technol 48:12937–12945. PubMedPubMedCentralCrossRefGoogle Scholar
  66. Lan J, Gou N, Rahman SM, Gao C, He M, Gu AZ (2016) A quantitative toxicogenomics assay for high-throughput and mechanistic genotoxicity assessment and screening of environmental pollutants. Environ Sci Technol 50:3202–3214. PubMedCrossRefGoogle Scholar
  67. Lewinska A, Miedziak B, Wnuk M (2014) Assessment of yeast chromosome XII instability: single chromosome comet assay. Fungal Genet Biol 63:9–16. PubMedCrossRefGoogle Scholar
  68. Lichtenberg-Fraté H, Schmitt M, Gellert G, Ludwig J (2003) A yeast-based method for the detection of cyto and genotoxicity. Toxicol In Vitro 17:709–716PubMedCrossRefGoogle Scholar
  69. Liu X, Kramer JA, Swaffield JC, Hu Y, Chai G, Wilson AG (2008) Development of a highthroughput yeast-based assay for detection of metabolically activated genotoxins. Mutat Res 653:63–69. PubMedCrossRefGoogle Scholar
  70. Lu Y, Tian Y, Wang R, Wu Q, Zhang Y, Li X (2015) Dual fluorescent protein-based bioassay system for the detection of genotoxic chemical substances in Saccharomyces cerevisiae. Toxicol Mech Methods 25:698–707. PubMedCrossRefGoogle Scholar
  71. Magdaleno A, Mendelson A, de Iorio AF, Rendina A, Moretton J (2008) Genotoxicity of leachates from highly polluted lowland river sediments destined for disposal in landfill. Waste Manag 28:2134–2139. PubMedCrossRefGoogle Scholar
  72. Malling HV (1971) Dimethylnitrosamine: formation of mutagenic compounds by interaction with mouse liver microsomes. Mutat Res 13:425–429PubMedCrossRefGoogle Scholar
  73. Marden A, Walmsley RM, Schweizer LM, Schweizer M (2006) Yeast-based assay for the measurement of positive and negative influences on microsatellite stability. FEMS Yeast Res 6:716–725. PubMedCrossRefGoogle Scholar
  74. McKinney JS, Sethi S, Tripp JD, Nguyen TN, Sanderson BA, Westmoreland JW, Resnick MA, Lewis LK (2013) A multistep genomic screen identifies new genes required for repair of DNA double-strand breaks in Saccharomyces cerevisiae. BMC Genomics 14:251. PubMedPubMedCentralCrossRefGoogle Scholar
  75. Miadoková E, Vlcková V, Duhová V, Trebatická M, Garajová L, Grolmus J, Podstavková S, Vlcek D (1992) Effects of supercypermethrin, a synthetic developmental pyrethroid, on four biological test systems. Mutat Res 280:161–168PubMedCrossRefGoogle Scholar
  76. Miloshev G, Mihaylov I, Anachkova B (2002) Application of the single cell gel electrophoresis on yeast cells. Mutat Res 513:69–74PubMedCrossRefGoogle Scholar
  77. Mizukami-Murata S, Iwahashi H, Kimura S, Nojima K, Sakurai Y, Saitou T, Fujii N, Murata Y, Suga S, Kitagawa K, Tanaka K, Endo S, Hoshi M (2010) Genome-wide expression changes in Saccharomyces cerevisiae in response to high-LET ionizing radiation. Appl Biochem Biotechnol 162:855–870. PubMedCrossRefGoogle Scholar
  78. Morita T, Iwamoto Y, Shimizu T, Masuzawa T, Yanagihara Y (1989) Mutagenicity tests with a permeable mutant of yeast on carcinogens showing false-negative in Salmonella assay. Chem Pharm Bull (Tokyo) 37:407–409CrossRefGoogle Scholar
  79. Moustacchi E (1980) Mutagenicity testing with eukaryotic microorganisms. Arch Toxicol 46:99–110PubMedCrossRefGoogle Scholar
  80. Murata J, Tada M, Iggo RD, Sawamura Y, Shinohe Y, Abe H (1997) Nitric oxide as a carcinogen: analysis by yeast functional assay of inactivating p53 mutations induced by nitric oxide. Mutat Res 379:211–218PubMedCrossRefGoogle Scholar
  81. Nemavarkar PS, Chourasia BK, Pasupathy K (2004) Detection of γ-irradiation induced DNA damage and radioprotection of compounds in yeast using comet assay. J Radiat Res 45:169–174PubMedCrossRefGoogle Scholar
  82. Ochi Y, Sugawara H, Iwami M, Tanaka M, Eki T (2011) Sensitive detection of chemical-induced genotoxicity by the Cypridina secretory luciferase reporter assay, using DNA repair-deficient strains of Saccharomyces cerevisiae. Yeast 28:265–278. PubMedCrossRefGoogle Scholar
  83. Oda Y, Nakamura S, Oki I, Kato T, Shinagawa H (1985) Evaluation of the new system (umu-test) for the detection of environmental mutagens and carcinogens. Mutat Res 147:219–229PubMedCrossRefGoogle Scholar
  84. Paget V, Lechevrel M, Sichel F (2008a) Acetaldehyde-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the FASAY (functional analysis of separated alleles in yeast). Mutat Res 652:12–19. PubMedCrossRefGoogle Scholar
  85. Paget V, Sichel F, Garon D, Lechevrel M (2008b) Aflatoxin B1-induced TP53 mutational pattern in normal human cells using the FASAY (Functional Analysis of Separated Alleles in Yeast). Mutat Res 656:55–61. PubMedCrossRefGoogle Scholar
  86. Paladino G, Weibel B, Sengstag C (1999) Heterocyclic aromatic amines efficiently induce mitotic recombination in metabolically competent Saccharomyces cerevisiae strains. Carcinogenesis 20:2143–2152PubMedCrossRefGoogle Scholar
  87. Parsons AB, Brost RL, Ding H, Li Z, Zhang C, Sheikh B, Brown GW, Kane PM, Hughes TR, Boone C (2004) Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nat Biotechnol 22:62–69. PubMedCrossRefGoogle Scholar
  88. Pellacani C, Buschini A, Furlini M, Poli P, Rossi C (2006) A battery of in vivo and in vitro tests useful for genotoxic pollutant detection in surface waters. Aquat Toxicol 77:1–10. PubMedCrossRefGoogle Scholar
  89. Pesheva M, Krastanova O, Staleva L, Dentcheva V, Hadzhitodorov M, Venkov P (2005) The Ty1 transposition assay: a new short-term test for detection of carcinogens. J Microbiol Methods 61:1–8. PubMedCrossRefGoogle Scholar
  90. Pesheva M, Krastanova O, Stamenova R, Kantardjiev D, Venkov P (2008) The response of Ty1 test to genotoxins. Arch Toxicol 82:779–785. PubMedCrossRefGoogle Scholar
  91. Pierce MK, Giroux CN, Kunz BA (1987) Development of a yeast system to assay mutational specificity. Mutat Res 182:65–74PubMedCrossRefGoogle Scholar
  92. 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 U S A 79:5971–5975PubMedPubMedCentralCrossRefGoogle Scholar
  93. Rajakrishna L, Unni SK, Subbiah M, Sadagopan S, Nair AR, Chandrappa R, Sambasivam G, Sukumaran SK (2014) Validation of a human cell based high-throughput genotoxicity assay ‘Anthem’s Genotoxicity screen’ using ECVAM recommended lists of genotoxic and non-genotoxic chemicals. Toxicol In Vitro 28:46–53. PubMedCrossRefGoogle Scholar
  94. Rank J, Syberg K, Jensen K (2009) Comet assay on tetraploid yeast cells. Mutat Res 673:53–58. PubMedCrossRefGoogle Scholar
  95. Reifferscheid G, Buchinger S (2010) Cell-based genotoxicity testing: genetically modified and genetically engineered bacteria in environmental genotoxicology. Adv Biochem Eng Biotechnol 118:85–111. PubMedGoogle Scholar
  96. Resnick MA, Mayer VW, Zimmermann FK (1986) The detection of chemically induced aneuploidy in Saccharomyces cerevisiae: an assessment of mitotic and meiotic systems. Mutat Res 167:47–60PubMedCrossRefGoogle Scholar
  97. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73:39–85. PubMedCrossRefGoogle Scholar
  98. Saner C, Weibel B, Würgler FE, Sengstag C (1996) Metabolism of promutagens catalyzed by Drosophila melanogaster CYP6A2 enzyme in Saccharomyces cerevisiae. Environ Mol Mutagen 27:46–58.<46::AID-EM7>3.0.CO;2-C PubMedCrossRefGoogle Scholar
  99. Schafer B, Neffgen A, Klinner U (2008) A novel yeast-based tool to detect mutagenic and recombinogenic effects simultaneously. Mutat Res 652:20–29. PubMedCrossRefGoogle Scholar
  100. Schiestl RH (1989) Nonmutagenic carcinogens induce intrachromosomal recombination in yeast. Nature 337:285–288. PubMedCrossRefGoogle Scholar
  101. Schiestl RH, Gietz RD, Mehta RD, Hastings PJ (1989) Carcinogens induce intrachromosomal recombination in yeast. Carcinogenesis 10:1445–1455PubMedCrossRefGoogle Scholar
  102. Schmitt M, Gellert G, Lichtenberg-Fraté H (2005) The toxic potential of an industrial effluent determined with the Saccharomyces cerevisiae-based assay. Water Res 39:3211–3218. PubMedCrossRefGoogle Scholar
  103. Sengstag C, Würgler FE (1994) DNA recombination induced by aflatoxin B1 activated by cytochrome P450 1A enzymes. Mol Carcinog 11:227–235PubMedCrossRefGoogle Scholar
  104. Sengstag C, Weibel B, Fasullo M (1996) Genotoxicity of aflatoxin B1: evidence for a recombination-mediated mechanism in Saccharomyces cerevisiae. Cancer Res 56:5457–5465PubMedGoogle Scholar
  105. Shahin MM, von Borstel RC (1976) Genetic activity of the antimicrobial food additives AF-2 and H-193 in Saccharomyces cerevisiae. Mutat Res 38:215–224PubMedCrossRefGoogle Scholar
  106. Simon JA, Szankasi P, Nguyen DK, Ludlow C, Dunstan HM, Roberts CJ, Jensen EL, Hartwell LH, Friend SH (2000) Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae. Cancer Res 60:328–333PubMedGoogle Scholar
  107. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191PubMedCrossRefGoogle Scholar
  108. Staleva L, Waltscheva L, Golovinsky E, Venkov P (1996) Enhanced cell permeability increases the sensitivity of a yeast test for mutagens. Mutat Res 370:81–89PubMedCrossRefGoogle Scholar
  109. Stehrer-Schmid P, Wolf HU (1995) Genotoxic evaluation of three heterocyclic N-methylcarbamate pesticides using the mouse bone marrow micronucleus assay and the Saccharomyces cerevisiae strains D7 and D61.M. Mutat Res 345:111–125PubMedCrossRefGoogle Scholar
  110. Suzuki H, Sakabe T, Hirose Y, Eki T (2017) Development and evaluation of yeast-based GFP and luciferase reporter assays for chemical-induced genotoxicity and oxidative damage. Appl Microbiol Biotechnol 101:659–671. PubMedCrossRefGoogle Scholar
  111. Svobodová K, Cajthaml T (2010) New in vitro reporter gene bioassays for screening of hormonal active compounds in the environment. Appl Microbiol Biotechnol 88:839–847. PubMedCrossRefGoogle Scholar
  112. Terziyska A, Waltschewa L, Venkov P (2000) A new sensitive test based on yeast cells for studying environmental pollution. Environ Pollut 109:43–52PubMedCrossRefGoogle Scholar
  113. Toussaint M, Levasseur G, Gervais-Bird J, Wellinger RJ, Elela SA, Conconi A (2006) A high-throughput method to measure the sensitivity of yeast cells to genotoxic agents in liquid cultures. Mutat Res 606:92–105. PubMedCrossRefGoogle Scholar
  114. Van Gompel J, Woestenborghs F, Beerens D, Mackie C, Cahill PA, Knight AW, Billinton N, Tweats DJ, Walmsley RM (2005) An assessment of the utility of the yeast GreenScreen assay in pharmaceutical screening. Mutagenesis 20:449–454. PubMedCrossRefGoogle Scholar
  115. van Leeuwen JS, Vermeulen NP, Vos JC (2012) Yeast as a humanized model organism for biotransformation-related toxicity. Curr Drug Metab 13:1464–1475PubMedCrossRefGoogle Scholar
  116. Walmsley RM, Billinton N, Heyer WD (1997) Green fluorescent protein as a reporter for the DNA damage-induced gene RAD54 in Saccharomyces cerevisiae. Yeast 13:1535–1545PubMedCrossRefGoogle Scholar
  117. Walsh L, Hastwell PW, Keenan PO, Knight AW, Billinton N, Walmsley RM (2005) Genetic modification and variations in solvent increase the sensitivity of the yeast RAD54-GFP genotoxicity assay. Mutagenesis 20:317–327. PubMedCrossRefGoogle Scholar
  118. Wei T, Zhang C, Xu X, Hanna M, Zhang X, Wang Y, Dai H, Xiao W (2013) Construction and evaluation of two biosensors based on yeast transcriptional response to genotoxic chemicals. Biosens Bioelectron 44:138–145. PubMedCrossRefGoogle Scholar
  119. Westerink WM, Stevenson JC, Lauwers A, Griffioen G, Horbach GJ, Schoonen WG (2009) Evaluation of the Vitotox and RadarScreen assays for the rapid assessment of genotoxicity in the early research phase of drug development. Mutat Res 676:113–130. PubMedCrossRefGoogle Scholar
  120. Westerink WM, Stevenson JC, Horbach GJ, Schoonen WG (2010) The development of RAD51C, Cystatin A, p53 and Nrf2 luciferase-reporter assays in metabolically competent HepG2 cells for the assessment of mechanism-based genotoxicity and of oxidative stress in the early research phase of drug development. Mutat Res 696:21–40. PubMedCrossRefGoogle Scholar
  121. Wu HI, Brown JA, Dorie MJ, Lazzeroni L, Brown JM (2004) Genome-wide identification of genes conferring resistance to the anticancer agents cisplatin, oxaliplatin, and mitomycin C. Cancer Res 64:3940–3948. PubMedCrossRefGoogle Scholar
  122. Zhang M, Liang Y, Zhang X, Xu Y, Dai H, Xiao W (2008) Deletion of yeast CWP genes enhances cell permeability to genotoxic agents. Toxicol Sci 103:68–76. PubMedCrossRefGoogle Scholar
  123. Zhang M, Hanna M, Li J, Butcher S, Dai H, Xiao W (2010) Creation of a hyperpermeable yeast strain to genotoxic agents through combined inactivation of PDR and CWP genes. Toxicol Sci 113:401–411. PubMedCrossRefGoogle Scholar
  124. Zhang M, Zhang C, Li J, Hanna M, Zhang X, Dai H, Xiao W (2011) Inactivation of YAP1 enhances sensitivity of the yeast RNR3-lacZ genotoxicity testing system to a broad range of DNA-damaging agents. Toxicol Sci 120:310–321. PubMedCrossRefGoogle Scholar
  125. Zimmermann FK, Kern R, Rasenberger H (1975) A yeast strain for simultaneous detection of induced mitotic crossing over, mitotic gene conversion and reverse mutation. Mutat Res 28:381–388CrossRefGoogle Scholar
  126. Zounková R, Odráška P, Doležalová L, Hilscherová K, Maršálek B, Bláha L (2007) Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals. Environ Toxicol Chem 26:2208–2214. PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Molecular Genetics Laboratory, Division of Bioscience and Biotechnology, Department of Environmental and Life SciencesToyohashi University of TechnologyToyohashiJapan

Personalised recommendations