{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:18:50Z","timestamp":1790468330714,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2008,10,16]],"date-time":"2008-10-16T00:00:00Z","timestamp":1224115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Baker\u2019s yeast, Saccharomyces cerevisiae, is the simplest and most well-known representative of eukaryotic cells and thus a convenient model organism for evaluating toxic effects in human cells and tissues. Yeast cell sensors are easy to maintain with short generation times, which makes the analytical method of assessing antifungal toxicity cheap and less-time consuming. In this work, the toxicity of test compounds was assessed in bioassays based on bioluminescence inhibition and on traditional growth inhibition on agar plates. The model organism in both tests was a modified S. cerevisiae sensor strain that produces light when provided with D-luciferin in an insect luciferase reporter gene activity assay. The bioluminescence assay showed toxic effects for yeast cell sensor of 5,6-benzo-flavone, rapamycin, nystatin and cycloheximide at concentrations of nM to \u00b5M. In addition, arsenic compounds, cadmium chloride, copper sulfate and lead acetate were shown to be potent non-specific inhibitors of the reporter organism described here. The results from a yeast agar diffusion assay correlated with the bioluminescence assay results.<\/jats:p>","DOI":"10.3390\/s8106433","type":"journal-article","created":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T10:14:52Z","timestamp":1224065692000},"page":"6433-6447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Real-time Monitoring of Non-specific Toxicity Using a Saccharomyces cerevisiae Reporter System"],"prefix":"10.3390","volume":"8","author":[{"given":"Anna-Liisa","family":"V\u00e4limaa","sequence":"first","affiliation":[{"name":"Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI- 33101 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anniina","family":"Kivist\u00f6","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI- 33101 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Virta","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry and Microbiology Division of Microbiology, P.O. Box 56, FI-00014, University of Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Karp","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI- 33101 Tampere, Finland"},{"name":"Biosensing Competence Centre (BCC), Tampere University of Technology, P.O. Box 541, FI- 33101 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2008,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/10643388309381702","article-title":"Bacterial and biochemical tests for assessing chemical toxicity in the aquatic environment: A review","volume":"13","author":"Bitton","year":"1983","journal-title":"CRC Crit. Rev. Environ Control"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0269-7491(02)00479-7","article-title":"Hormesis and stage specific toxicity induced by cadmium in an insect model, the queen blowfly, Phormia regina Meig","volume":"124","author":"Nascarella","year":"2003","journal-title":"Environ. Pollut."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.tiv.2007.06.012","article-title":"Acute and subacute toxic effects produced by microcystin-YR on the fish cell lines RTG-2 and PLHC-1","volume":"21","author":"Pichardo","year":"2007","journal-title":"Toxicol. in Vitro"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.scitotenv.2007.07.057","article-title":"Toxicological assessment of indium nitrate on aquatic organisms and investigation of the effects on the PLHC-1 fish cell line","volume":"387","author":"Zurita","year":"2007","journal-title":"Sci. Total Environ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ejpb.2005.09.011","article-title":"In vitro toxicity to breast cancer cells of microsphere-delivered mitomycin C and its combination with doxorubicin","volume":"62","author":"Cheung","year":"2006","journal-title":"Eur. J. Pharmaceut. Biopharmaceut."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/BF00212137","article-title":"Comparison of microbial bioassays for the detection of metal toxicity","volume":"25","author":"Codina","year":"1993","journal-title":"Arch. Environ. Contam. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1006\/taap.2002.9395","article-title":"In Vitro Estrogen Reseptor Binding of PCBs: Measured activity and detection of hydroxylated metabolites in a recombinant yeast assay","volume":"180","author":"Layton","year":"2002","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0079-6603(08)60826-0","article-title":"Genetic regulation of phospholipid metabolism: yeast as a model eukaryote","volume":"61","author":"Henry","year":"1998","journal-title":"Prog. Nucleic Acid Res. Mol. Biol."},{"key":"ref_9","unstructured":"Amberg, D.C., Burke, D.J., and Strathern, J.N. (2005). Methods in yeast genetics. A Cold Spring Harbor Laboratory Course Manual, Cold Spring Harbor Laboratory Press."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1365-2443.2005.00847.x","article-title":"Mutational analysis of the multidrug resistance ABC transporter Pdr5p with altered drug specificity","volume":"10","author":"Mikoshki","year":"2005","journal-title":"Genes Cells"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/0731-7085(95)01709-7","article-title":"Toxicity order of cholanic acids using an immobilised cell biosensor","volume":"14","author":"Campanella","year":"1996","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/BF01701786","article-title":"Rapid toxicity testing based on yeast respiratory activity","volume":"44","author":"Haubenstricker","year":"1990","journal-title":"Bull. Environ. Contam. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF01129205","article-title":"A comparison of effects of chromate, molybdate and cadmium oxide on respiration in the yeast Saccharomyces cerevisiae","volume":"2","author":"Henderson","year":"1989","journal-title":"Biol. Metals"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0168-1656(96)01399-5","article-title":"Microbial cyanide sensor for monitoring river water","volume":"48","author":"Ikebukuro","year":"1996","journal-title":"J. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1128\/aem.56.7.2114-2119.1990","article-title":"Effects of cyclohexane, an industrial solvent, on the yeast Saccharomyces cerevisiae and on isolated yeast mitochondria","volume":"56","author":"Uribe","year":"1990","journal-title":"Appl. Environ. Mirobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.mrgentox.2006.03.006","article-title":"A high-throughput method to measure the sensitivity of yeast cells to genotoxic agents in liquid cultures","volume":"606","author":"Toussaint","year":"2006","journal-title":"Mutat. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ecoenv.2004.06.002","article-title":"Phenotypic yeast growth analysis for chronic toxicity testing","volume":"59","author":"Schmitt","year":"2004","journal-title":"Ecotoxicol. Environ. Safety"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/(SICI)1097-0061(199712)13:16<1535::AID-YEA221>3.0.CO;2-2","article-title":"Green fluorescent protein as a reporter for the DNA damage-induced gene RAD54 in Saccharomyces cerevisiae","volume":"13","author":"Walmsley","year":"1997","journal-title":"Yeast"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.scitotenv.2005.01.029","article-title":"Lead and Cu in contaminated urban soils: extraction with chemical reagents and bioluminescent bacteria and yeast","volume":"350","author":"Peltola","year":"2005","journal-title":"Sci. Total Environ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1128\/AEM.66.4.1676-1679.2000","article-title":"Design and application of a biosensor for monitoring toxicity of compounds to eukaryotes","volume":"66","author":"Hollis","year":"2000","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.chemosphere.2005.01.080","article-title":"Bioluminescence yeast assays for detecting estrogenic and androgenic activity in different matrices","volume":"61","author":"Leskinen","year":"2005","journal-title":"Chemosphere"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/tox.10079","article-title":"Acute toxicity, mutagenicity, and estrogenicity of biodegradation products of bisphenol-A","volume":"17","author":"Ike","year":"2002","journal-title":"Environ. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/etc.5620150303","article-title":"Estrogenic activity of surfactants and some of their degradation products assessed using a recombinant yeast screen","volume":"15","author":"Routledge","year":"1996","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1289\/ehp.01109691","article-title":"Optimization of a yeast estrogen screen and its applicability to study the release of estrogenic isoflavones from a soygerm powder","volume":"109","author":"Vanderperren","year":"2001","journal-title":"Environ. Health Pers."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1016\/j.watres.2004.04.021","article-title":"Rapid loss of estrogenicity of steroid estrogens by UVA photolysis and photocatalysis over an immobilized titanium dioxide catalyst","volume":"38","author":"Colemana","year":"2004","journal-title":"Water Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1016\/j.bios.2004.10.018","article-title":"A new recombinant cell-based bioluminescent assay for sensitive androgen-like compound detection","volume":"20","author":"Michelini","year":"2005","journal-title":"Biosens. Bioelectron."},{"key":"ref_27","first-page":"311","article-title":"A yeast strain biosensor to detect cell wall-perturbing agents","volume":"133","author":"Nombela","year":"2007","journal-title":"J. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gould, S.J., Keller, G.-A., and Subramani, S. (1988). Identification of peroxisomal targeting signals located at the carboxy terminus of four peroxisomal proteins. J. Cell Biol., 897\u2013905.","DOI":"10.1083\/jcb.107.3.897"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/yea.1024","article-title":"One-step measurement of firefly luciferase activity in yeast","volume":"20","author":"Leskinen","year":"2003","journal-title":"Yeast"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0166-445X(97)00069-6","article-title":"Biotransformation enzymes and their induction by \u03b2-naphtoflavone in adult sea bass (Dicentrarchus labrax)","volume":"41","author":"Novi","year":"1998","journal-title":"Aquat. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Crespo, J.L., and Hall, M.N. (2002). Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rew., 579\u2013591.","DOI":"10.1128\/MMBR.66.4.579-591.2002"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1128\/AAC.7.2.121","article-title":"Nystatin-induced changes in Saccharomyces cerevisiae","volume":"7","author":"Venables","year":"1975","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1271\/bbb.63.1075","article-title":"Nystatin effects on vacuolar function in Saccharomyces cerevisiae","volume":"96","author":"Bhuiyan","year":"1999","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/BF00499967","article-title":"Continous flow method for extraction and bioluminescence assay of ATP on baker's yeast","volume":"15","author":"Siro","year":"1982","journal-title":"Eur. J. Appl. Microbiol. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.mib.2006.08.006","article-title":"The world of subinhibitory antibiotic concentrations","volume":"9","author":"Davies","year":"2006","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7988","DOI":"10.1128\/JB.00791-06","article-title":"Transcription modulation of Salmonella enterica serovar Typhimurium promoters by sub-MIC levels of rifampin","volume":"188","author":"Yim","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jbiotec.2006.06.019","article-title":"Intracellular redox equilibrium and growth phase affect the performance of luciferase-based biosensors","volume":"127","author":"Galluzzi","year":"2007","journal-title":"J. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.watres.2003.08.027","article-title":"Toxicity of anionic detergents determined by Saccharomyces cerevisiae microarray analysis","volume":"38","author":"Sirisattha","year":"2004","journal-title":"Water Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0378-1119(01)00558-3","article-title":"Novel target genes of the yeast regulator Pdr1p: a contribution of the TPO1 gene in resistance to quinidine and other drugs","volume":"272","author":"Jonniaux","year":"2001","journal-title":"Gene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0014-5793(04)00046-8","article-title":"Expression regulation of the yeast PDR5 ATP-binding cassette (ABC) transporter suggests a role in cellular detoxification during the exponential growth phase","volume":"559","author":"Mamnum","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0005-2736(99)00160-1","article-title":"Inventory and function of yeast ABC proteins: about sex, stress, pleiotropic drug and heavy metal resistance","volume":"1461","author":"Bauer","year":"1999","journal-title":"Biochim. Biophys Acta."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.biochi.2006.05.016","article-title":"Metal(loid)s and radionuclides cytotoxicity in Saccharomyces verevisiae. Role of YCF1, gluthatione and effect of buthionine sulfoximine","volume":"88","author":"Ansoborlo","year":"2006","journal-title":"Biochimie"},{"key":"ref_43","first-page":"1860","article-title":"Early expression of yeast genes affected by chemical stress","volume":"124","author":"Lelandais","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1007\/s002530051457","article-title":"Microbial heavy-metal resistance","volume":"51","author":"Nies","year":"1999","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5001","DOI":"10.1073\/pnas.96.9.5001","article-title":"Pathways of As(III) detoxification in Saccharomyces cerevisiae","volume":"96","author":"Ghosh","year":"1999","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/BF00436082","article-title":"Protonation of ketoconazole in relation to fungistatic activity","volume":"116","author":"Beggs","year":"1991","journal-title":"Mycopathology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1128\/AAC.23.1.105","article-title":"Effects of pH on the activity of ketoconazole against Candida albicans","volume":"23","author":"Minigawa","year":"1983","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/8\/10\/6433\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:21:03Z","timestamp":1760221263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/8\/10\/6433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,16]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2008,10]]}},"alternative-id":["s8106433"],"URL":"https:\/\/doi.org\/10.3390\/s8106433","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,16]]}}}