Detection of Organic Compounds with Whole-Cell Bioluminescent Bioassays

  • Tingting Xu
  • Dan Close
  • Abby Smartt
  • Steven Ripp
  • Gary Sayler
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 144)


Natural and manmade organic chemicals are widely deposited across a diverse range of ecosystems including air, surface water, groundwater, wastewater, soil, sediment, and marine environments. Some organic compounds, despite their industrial values, are toxic to living organisms and pose significant health risks to humans and wildlife. Detection and monitoring of these organic pollutants in environmental matrices therefore is of great interest and need for remediation and health risk assessment. Although these detections have traditionally been performed using analytical chemical approaches that offer highly sensitive and specific identification of target compounds, these methods require specialized equipment and trained operators, and fail to describe potential bioavailable effects on living organisms. Alternatively, the integration of bioluminescent systems into whole-cell bioreporters presents a new capacity for organic compound detection. These bioreporters are constructed by incorporating reporter genes into catabolic or signaling pathways that are present within living cells and emit a bioluminescent signal that can be detected upon exposure to target chemicals. Although relatively less specific compared to analytical methods, bioluminescent bioassays are more cost-effective, more rapid, can be scaled to higher throughput, and can be designed to report not only the presence but also the bioavailability of target substances. This chapter reviews available bacterial and eukaryotic whole-cell bioreporters for sensing organic pollutants and their applications in a variety of sample matrices.

Graphical Abstract


Bacterial luciferase Bioavailability Bioreporter Bioluminescence BTEX Dioxin Endocrine disruptors Environmental monitoring Firefly luciferase Hydrocarbon PAH PCB 



Aryl hydrocarbon receptor


Androgen receptor


Androgen response element


AhR nuclear translocator




Benzene, toluene, ethylbenzene, and xylene


Chemical-activated luciferase expression






Dioxin-responsive element




Endocrine disrupting chemical




Estrogen receptor


Estrogen response element


Gas chromatography


Glucocorticoid receptor


High-performance liquid chromatography


Mass spectrometry


Polycyclic aromatic hydrocarbon


Polychlorinated biphenyls


Polychlorinated dibenzo-p-dioxin


Polychlorinated dibenzofuran


Photomultiplier tube


Progesterone receptor




1,1,1 trichloroethane






Thyroid receptor


  1. 1.
    Yeh BJ, Lim WA (2007) Synthetic biology: lessons from the history of synthetic organic chemistry. Nat Chem Biol 3:521–525Google Scholar
  2. 2.
    Snyder R (2000) Overview of the toxicology of benzene. J Toxicol Env Health-Pt A 61:339–346Google Scholar
  3. 3.
    Dawson JJC, Iroegbu CO, Maciel H, Paton GI (2008) Application of luminescent biosensors for monitoring the degradation and toxicity of BTEX compounds in soils. J Appl Microbiol 104:141–151Google Scholar
  4. 4.
    Girotti S, Bolelli L, Roda A, Gentilomi G, Musiani M (2002) Improved detection of toxic chemicals using bioluminescent bacteria. Anal Chim Acta 471:113–120Google Scholar
  5. 5.
    Xu T, Close DM, Sayler GS, Ripp SA (2013) Genetically modified whole-cell bioreporters for environmental assessment. Ecol Indic 28:125–141Google Scholar
  6. 6.
    Williams PA, Murray K (1974) Metabolism of benzoate and methylbenzoates by Pseudomonas putida mt-2: evidence for existance of a TOL plasmid. J Bacteriol 120:416–423Google Scholar
  7. 7.
    Franklin FCH, Bagdasarian M, Bagdasarian MM, Timmis KN (1981) Molecular and functional analysis of the TOL Plasmid pWWO from Pseudomonas putida and cloning of genes for the enitre regulated aromatic ring meta-cleavage pathway. Proc Natl Acad Sci USA 78:7458–7462Google Scholar
  8. 8.
    Worsey MJ, Franklin FCH, Williams PA (1978) Regulation of degradative pathway enzymes coded for by TOL plasmid pWWO from Pseudomonas putida mt-2. J Bacteriol 134:757–764Google Scholar
  9. 9.
    Worsey MJ, Williams PA (1975) Metabolism of toluene and xylenes by Pseudomonas putida mt-2: evidence for a new function of TOL plasmid. J Bacteriol 124:7–13Google Scholar
  10. 10.
    Ramos JL, Marques S, Timmis KN (1997) Transcriptional control of the Pseudomonas tol plasmid catabolic operons is achieved through an interplay of host factors and plasmid-encoded regulators. An Rev Microbiol 51:341–373Google Scholar
  11. 11.
    Li Y-F, Li F-Y, Ho C-L, Liao VH-C (2008) Construction and comparison of fluorescence and bioluminescence bacterial biosensors for the detection of bioavailable toluene and related compounds. Environ Pollut 152:123–129Google Scholar
  12. 12.
    Urbanczyk H, Ast JC, Higgins MJ, Carson J, Dunlap PV (2007) Reclassification of Vibrio fischeri, Vibrio logei, Vibrio salmonicida and Vibrio wodanis as Aliivibrio fischeri gen. nov., comb. nov., Aliivibrio logei comb. nov., Aliivibrio salmonicida comb. nov and Aliivibrio wodanis comb. nov. Int J Syst Evol Microbiol 57:2823–2829Google Scholar
  13. 13.
    Willardson BM, Wilkins JF, Rand TA, Schupp JM, Hill KK, Keim P, Jackson PJ (1998) Development and testing of a bacterial biosensor for toluene-based environmental contaminants. Appl Environ Microbiol 64:1006–1012Google Scholar
  14. 14.
    Tecon R, Beggah S, Czechowska K, Sentchilo V, Chronopoulou PM, McGenity TJ, van der Meer JR (2010) Development of a multistrain bacterial bioreporter platform for the monitoring of hydrocarbon contaminants in marine environments. Environ Sci Technol 44:1049–1055Google Scholar
  15. 15.
    Applegate BM, Kehrmeyer SR, Sayler GS (1998) A chromosomally based tod-luxCDABE whole-cell reporter for benzene, toluene, ethybenzene, and xylene (BTEX) sensing. Appl Environ Microbiol 64:2730–2735Google Scholar
  16. 16.
    Zylstra G, McCombie W, Gibson D, Finette B (1988) Toluene degradation by Pseudomonas putida F1: genetic organization of the tod operon. Appl Environ Microbiol 54:1498–1503Google Scholar
  17. 17.
    Wang Y, Rawlings M, Gibson DT, Labbe D, Bergeron H, Brousseau R, Lau PCK (1995) Identification of a membrane protein and a truncated LysR type regulator associated with the toluene degradation pathway in Pseudomonas putida F1. Mol Gen Genet 246:570–579Google Scholar
  18. 18.
    Kuncova G, Pazlarova J, Hlavata A, Ripp S, Sayler GS (2011) Bioluminescent bioreporter Pseudomonas putida TVA8 as a detector of water pollution. Operational conditions and selectivity of free cells sensor. Ecol Indic 11:882–887Google Scholar
  19. 19.
    Stiner L, Halverson LJ (2002) Development and characterization of a green fluorescent protein-based bacterial biosensor for bioavailable toluene and related compounds. Appl Environ Microbiol 68:1962–1971Google Scholar
  20. 20.
    Bhattacharyya J, Read D, Amos S, Dooley S, Killham K, Paton GI (2005) Biosensor-based diagnostics of contaminated groundwater: assessment and remediation strategy. Environ Pollut 134:485–492Google Scholar
  21. 21.
    Eaton RW, Timmis KN (1986) Characterization of a plasmid-specified pathway for catabolism of isopropylbenzne in Pseudomonas putida RE204. J Bacteriol 168:123–131Google Scholar
  22. 22.
    Selifonova OV, Eaton RW (1996) Use of an ipb-lux fusion to study regulation of the isopropylbenzene catabolism operon of Pseudomonas putida RE204 and to detect hydrophobic pollutants in the environment. Appl Environ Microbiol 62:778–783Google Scholar
  23. 23.
    Mumtaz MM, George JD, Gold KW, Cibulas W, Derosa CT (1996) ATSDR evaluation of health effects of chemicals. 4. Polycyclic aromatic hydrocarbons (PAHs): understanding a complex problem. Toxicol Ind Health 12:742–971Google Scholar
  24. 24.
    Grund AD, Gunsalus IC (1983) Cloning of genes for naphthalene metabolism in Pseudomonas putida. J Bacteriol 156:89–94Google Scholar
  25. 25.
    Burlage RS, Sayler GS, Larimer F (1990) Monitoring of naphthalene catabolism by bioluminescence with nah-lux transcriptional fusions. J Bacteriol 172:4749–4757Google Scholar
  26. 26.
    Dorn JG, Brusseau ML, Maier RM (2005) Real-time, in situ monitoring of bioactive zone dynamics in heterogeneous systems. Environ Sci Technol 39:8898–8905Google Scholar
  27. 27.
    Dorn JG, Frye RJ, Maier RM (2003) Effect of temperature, pH, and initial cell number on luxCDABE and nah gene expression during naphthalene and salicylate catabolism in the bioreporter organism Pseudomonas putida RB1353. Appl Environ Microbiol 69:2209–2216Google Scholar
  28. 28.
    Dorn JG, Mahal MK, Brusseau ML, Maier RM (2004) Employing a novel fiber optic detection system to monitor the dynamics of in situ lux bioreporter activity in porous media: system performance update. Anal Chim Acta 525:63–74Google Scholar
  29. 29.
    King JMH, Digrazia PM, Applegate B, Burlage R, Sanseverino J, Dunbar P, Larimer F, Sayler GS (1990) Rapid, sensitive bioluminescent reporter technology for naphthalene exposure and biodegradation. Science 249:778–781Google Scholar
  30. 30.
    Trogl J, Chauhan A, Ripp S, Layton AC, Kuncova G, Sayler GS (2012) Pseudomonas fluorescens HK44: lessons learned from a model whole-cell bioreporter with a broad application history. Sensors 12:1544–1571Google Scholar
  31. 31.
    Valdman E, Gutz IGR (2008) Bioluminescent sensor for naphthalene in air: Cell immobilization and evaluation with a dynamic standard atmosphere generator. Sens Actuator B-Chem 133:656–663Google Scholar
  32. 32.
    Ripp S, Nivens DE, Ahn Y, Werner C, Jarrell J, Easter JP, Cox CD, Burlage RS, Sayler GS (2000) Controlled field release of a bioluminescent genetically engineered microorganism for bioremediation process monitoring and control. Environ Sci Technol 34:846–853Google Scholar
  33. 33.
    Sayler GS, Ripp S (2000) Field applications of genetically engineered microorganisms for bioremediation processes. Curr Opin Biotechnol 11:286–289Google Scholar
  34. 34.
    Laurie AD, Lloyd-Jones G (1999) The phn genes of Burkholderia sp. strain RP007 constitute a divergent gene cluster for polycyclic aromatic hydrocarbon catabolism. J Bacteriol 181:531–540Google Scholar
  35. 35.
    Chakrabarty A, Chou G, Gunsalus I (1973) Genetic regulation of octane dissimilation plasmid in Pseudomonas. Proc Natl Acad Sci USA 70:1137–1140Google Scholar
  36. 36.
    Eggink G, Engel H, Meijer W, Otten J, Kingma J, Witholt B (1988) Alkane utilization in Pseudomonas oleovorans. Structure and function of the regulatory locus alkR. J Biol Chem 263:13400–13405Google Scholar
  37. 37.
    Sticher P, Jaspers MCM, Stemmler K, Harms H, Zehnder AJB, van der Meer JR (1997) Development and characterization of a whole-cell bioluminescent sensor for bioavailable middle-chain alkanes in contaminated groundwater samples. Appl Environ Microbiol 63:4053–4060Google Scholar
  38. 38.
    Owen DJ, Eggink G, Hauer B, Kok M, McBeth DL, Yang YL, Shapiro JA (1984) Physical structure, genetic content and expression of the alkBAC operon. Mol Gen Genet 197:373–383Google Scholar
  39. 39.
    Minak-Bernero V, Bare RE, Haith CE, Grossman MJ (2004) Detection of alkanes, alcohols, and aldehydes using bioluminescence. Biotechnol Bioeng 87:170–177Google Scholar
  40. 40.
    Bosetti A, van Beilen JB, Preusting H, Lageveen RG, Witholt B (1992) Production of primary aliphatic alcohols with a recombinant Pseudomonas strain, encoding the alkane hydroxylase enzyme system. Enzyme Microb Technol 14:702–708Google Scholar
  41. 41.
    Francisco W, Abu-Soud H, Baldwin T, Raushel F (1993) Interaction of aldehyde substrate and inhibitors to bacterial luciferase. J Biol Chem 268:24734–24741Google Scholar
  42. 42.
    Atlas RM, Hazen TC (2011) Oil biodegradation and bioremediation: a tale of the two worst spills in U.S. history. Environ Sci Technol 45:6709–6715Google Scholar
  43. 43.
    Zhang D, He Y, Wang Y, Wang H, Wu L, Aries E, Huang WE (2012) Whole-cell bacterial bioreporter for actively searching and sensing of alkanes and oil spills. Microb Biotechnol 5:87–97Google Scholar
  44. 44.
    Zhang DY, Fakhrullin RF, Ozmen M, Wang H, Wang J, Paunov VN, Li GH, Huang WE (2011) Functionalization of whole-cell bacterial reporters with magnetic nanoparticles. Microb Biotechnol 4:89–97Google Scholar
  45. 45.
    Kumari R, Tecon R, Beggah S, Rutler R, Arey JS, van der Meer JR (2011) Development of bioreporter assays for the detection of bioavailability of long-chain alkanes based on the marine bacterium Alcanivorax borkumensis strain SK2. Environ Microbiol 13:2808–2819Google Scholar
  46. 46.
    van Hylckama Vlieg JET, Janssen DB (2001) Formation and detoxification of reactive intermediates in the metabolism of chlorinated ethenes. J Biotechnol 85:81–102Google Scholar
  47. 47.
    Arcangeli J-P, Arvin E (1997) Modeling of the cometabolic biodegradation of trichloroethylene by toluene-oxidizing bacteria in a biofilm system. Environ Sci Technol 31:3044–3052Google Scholar
  48. 48.
    Sponza DT (2003) Toxicity and treatability of carbontetrachloride and tetrachloroethylene in anaerobic batch cultures. Int Biodeterior Biodegrad 51:119–127Google Scholar
  49. 49.
    Shingleton JT, Applegate BM, Nagel AC, Bienkowski PR, Sayler GS (1998) Induction of the tod operon by trichloroethylene in Pseudomonas putida TVA8. Appl Environ Microbiol 64:5049–5052Google Scholar
  50. 50.
    Phoenix P, Keane A, Patel A, Bergeron H, Ghoshal S, Lau P (2003) Characterization of a new solvent-responsive gene locus in Pseudomonas putida F1 and its functionalization as a versatile biosensor. Environ Microbiol 5:1309–1327Google Scholar
  51. 51.
    Lopes N, Hawkins SA, Jegier P, Menn F-M, Sayler GS, Ripp S (2012) Detection of dichloromethane with a bioluminescent (lux) bacterial bioreporter. J Ind Microbiol Biotechnol 39:45–53Google Scholar
  52. 52.
    Furukawa K, Fujihara H (2008) Microbial degradation of polychlorinated biphenyls: Biochemical and molecular features. J Biosci Bioeng 105:433–449Google Scholar
  53. 53.
    Layton AC, Muccini M, Ghosh MM, Sayler GS (1998) Construction of a bioluminescent reporter strain to detect polychlorinated biphenyls. Appl Environ Microbiol 64:5023–5026Google Scholar
  54. 54.
    Bradley C, Berube PR (2008) Characterization of anionic surfactant-induced toxicity in a primary effluent. J Environ Eng Sci 7:63–70Google Scholar
  55. 55.
    Layton AC, Gregory B, Schultz TW, Sayler GS (1999) Validation of genetically engineered bioluminescent surfactant resistant bacteria as toxicity assessment tools. Ecotox Environ Safe 43:222–228Google Scholar
  56. 56.
    Park SH, Lee K, Chae JC, Kim CK (2004) Construction of transformant reporters carrying fused genes using pcbC promoter of Pseudomonas sp DJ-12 for detection of aromatic pollutants. Environ Monit Assess 92:241–251Google Scholar
  57. 57.
    Jaspers MCM, Suske WA, Schmid A, Goslings DAM, Kohler HPE, van der Meer JR (2000) HbpR, a new member of the XylR/DmpR subclass within the NtrC family of bacterial transcriptional activators, regulates expression of 2-hydroxybiphenyl metabolism in Pseudomonas azelaica HBP1. J Bacteriol 182:405–417Google Scholar
  58. 58.
    Turner K, Xu S, Pasini P, Deo S, Bachas L, Daunert S (2007) Hydroxylated polychlorinated biphenyl detection based on a genetically engineered bioluminescent whole-cell sensing system. Anal Chem 79:5740–5745Google Scholar
  59. 59.
    Tropel D, Bahler A, Globig K, van der Meer JR (2004) Design of new promoters and of a dual-bioreporter based on cross-activation by the two regulatory proteins XylR and HbpR. Environ Microbiol 6:1186–1196Google Scholar
  60. 60.
    Krastanov A, Alexieva Z, Yemendzhiev H (2013) Microbial degradation of phenol and phenolic derivatives. Eng Life Sci 13:76–87Google Scholar
  61. 61.
    Shingler V, Franklin FCH, Tsuda M, Holroyd D, Bagdasarian M (1989) Molecular analysis of a plasmid-encoded phenol hydroxylase from Pseudomonas CF600. J Gen Microbiol 135:1083–1092Google Scholar
  62. 62.
    Shingler V, Bartilson M, Moore T (1993) Cloning and nucleotide-sequencing of the gene encoding the positive regulator (DmpR) of the phenol catabolic pathway encoded by PVI150 and identification of DmpR as a member of the NtrC family of transcriptional activators. J Bacteriol 175:1596–1604Google Scholar
  63. 63.
    Leedjarv A, Ivask A, Virta M, Kahru A (2006) Analysis of bioavailable phenols from natural samples by recombinant luminescent bacterial sensors. Chemosphere 64:1910–1919Google Scholar
  64. 64.
    Wise AA, Kuske CR (2000) Generation of novel bacterial regulatory proteins that detect priority pollutant phenols. Appl Environ Microbiol 66:163–169Google Scholar
  65. 65.
    Gupta S, Saxena M, Saini N, Mahmooduzzafar, Kumar R, Kumar A (2012) An effective strategy for a whole-cell biosensor based on putative effector interaction site of the regulatory DmpR protein. PLoS ONE 7: e43527Google Scholar
  66. 66.
    Ehrt S, Schirmer F, Hillen W (1995) Genetic organization, nucleotide sequence and regulation of expression of genes encoding phenol hydroxylase and catechol 1,2-dioxygenase in Acinetobacter calcoaceticus NCIB8250. Mol Microbiol 18:13–20Google Scholar
  67. 67.
    Abd-El-Haleem D, Ripp S, Scott C, Sayler GS (2002) A luxCDABE-based bioluminescent bioreporter for the detection of phenol. J Ind Microbiol Biotechnol 29:233–237Google Scholar
  68. 68.
    Zaki S, Abd-El-Haleem D, Abulhamd A, Elbery H, AbuElreesh G (2008) Influence of phenolics on the sensitivity of free and immobilized bioluminescent Acinetobacter bacterium. Microbiol Res 163:277–285Google Scholar
  69. 69.
    Wiles S, Whiteley AS, Philp JC, Bailey MJ (2003) Development of bespoke bioluminescent reporters with the potential for in situ deployment within a phenolic-remediating wastewater treatment system. J Microbiol Methods 55:667–677Google Scholar
  70. 70.
    Ghosh SK, Doctor PB (1992) Toxicity screening of phenol using Microtox. Environ Toxicol Water Quality 7:157–163Google Scholar
  71. 71.
    Ismailov AD, Pogosyan SI, Mitrofanova TI, Egorov NS, Netrusov AI (2000) Bacterial bioluminescence inhibition by chlorophenols. Appl Biochem Microbiol 36:404–408Google Scholar
  72. 72.
    Kudryasheva N, Vetrova E, Kuznetsov A, Kratasyuk V, Stom D (2002) Bioluminescence assays: Effects of quinones and phenols. Ecotox Environ Safe 53:221–225Google Scholar
  73. 73.
    Berglind R, Leffler P, Sjostrom M (2010) Interactions between pH, potassium, calcium, bromide, and phenol and their effects on the bioluminescence of Vibrio fischeri. J Toxicol Env Health-Pt A 73:1102–1112Google Scholar
  74. 74.
    Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC (2009) Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocr Rev 30:293–342Google Scholar
  75. 75.
    Alcock RE, Behnisch PA, Jones KC, Hagenmaier H (1998) Dioxin-like PCBs in the environment—human exposure and the significance of sources. Chemosphere 37:1457–1472Google Scholar
  76. 76.
    Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO (1995) The E-SCREEN assay as a tool to identify estrogens—an update on estrogenic environmental pollutants. Environ Health Perspect 103:113–122Google Scholar
  77. 77.
    Van den Berg M, Birnbaum L, Bosveld A, Brunström B, Cook P, Feeley M, Giesy JP, Hanberg A, Hasegawa R, Kennedy SW (1998) Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environ Health Perspect 106:775–792Google Scholar
  78. 78.
    Ahlborg UG, Brouwer A, Fingerhut MA, Jacobson JL, Jacobson SW, Kennedy SW, Kettrup AA, Koeman JH, Poiger H, Rappe C (1992) Impact of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls on human and environmental health, with special emphasis on application of the toxic equivalency factor concept. Environ Toxicol Pharmacol 228:179–199Google Scholar
  79. 79.
    Peterson RE, Theobald HM, Kimmel GL (1993) Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. Crit Rev Toxicol 23:283–335Google Scholar
  80. 80.
    Garrison P, Tullis K, Aarts J, Brouwer A, Giesy J, Denison M (1996) Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. Toxicol Sci 30:194–203Google Scholar
  81. 81.
    Safe SH (1995) Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Pharmacol Ther 67:247–281Google Scholar
  82. 82.
    Postlind H, Vu T, Tukey R, Quattrochi LC (1993) Response of human CYP1-luciferase plasmids to 2,3,7,8-tetrachlorodibenzo-p-dioxin and polycyclic aromatic hydrocarbons. Toxicol Appl Pharmacol 118:255–262Google Scholar
  83. 83.
    Murk AJ, Legler J, Denison MS, Giesy JP, vandeGuchte C, Brouwer A (1996) Chemical-activated luciferase gene expression (CALUX): a novel in vitro bioassay for Ah receptor active compounds in sediments and pore water. Fundam Appl Toxicol 33:149–160Google Scholar
  84. 84.
    Murk AJ, Leonards PEG, Bulder AS, Jonas AS, Rozemeijer MJC, Denison MS, Koeman JH, Brouwer A (1997) The CALUX (chemical-activated luciferase expression) assay adapted and validated for measuring TCDD equivalents in blood plasma. Environ Toxicol Chem 16:1583–1589Google Scholar
  85. 85.
    Bovee TFH, Hoogenboom LAP, Hamers ARM, Traag WA, Zuidema T, Aarts J, Brouwer A, Kuiper HA (1998) Validation and use of the CALUX-bioassay for the determination of dioxins and PCBs in bovine milk. Food Addit Contam 15:863–875Google Scholar
  86. 86.
    Cederberg T, Laier P, Vinggaard AM (2002) Screening of food samples for dioxin levels: comparison of GC-MS determination with the CALUX bioassay. Organohalogen Compd 58:409–412Google Scholar
  87. 87.
    Tsutsumi T, Amakura Y, Nakamura M, Brown DJ, Clark GC, Sasaki K, Toyoda M, Maitani T (2003) Validation of the CALUX bioassay for the screening of PCDD/Fs and dioxin-like PCBs in retail fish. Analyst 128:486–492Google Scholar
  88. 88.
    Van Overmeire I, Carbonnelle S, Van Loco J, Roos P, Brown D, Chu M, Clark G, Goeyens L (2002) Validation of the CALUX bioassay: quantitative screening approach. Organohalogen Compd 58:353–356Google Scholar
  89. 89.
    Pauwels A, Cenijn PH, Schepens P, Brouwer A (2000) Comparison of chemical-activated luciferase gene expression bioassay and gas chromatography for PCB determination in human serum and follicular fluid. Environ Health Perspect 108:553–557Google Scholar
  90. 90.
    Van Wouwe N, Windal I, Vanderperren H, Eppe G, Xhrouet C, Massart A-C, Debacker N, Sasse A, Baeyens W, De Pauw E (2004) Validation of the CALUX bioassay for PCDD/F analyses in human blood plasma and comparison with GC-HRMS. Talanta 63:1157–1167Google Scholar
  91. 91.
    Leskinen P, Hilscherova K, Sidlova T, Kiviranta H, Pessala P, Salo S, Verta M, Virta M (2008) Detecting AhR ligands in sediments using bioluminescent reporter yeast. Biosens Bioelectron 23:1850–1855Google Scholar
  92. 92.
    Windal I, Denison MS, Birnbaum LS, Van Wouwe N, Baeyens W, Goeyens L (2005) Chemically activated luciferase gene expression (CALUX) cell bioassay analysis for the estimation of dioxin-like activity: critical parameters of the CALUX procedure that impact assay results. Environ Sci Technol 39:7357–7364Google Scholar
  93. 93.
    Besselink HT, Schipper C, Klamer H, Leonards P, Verhaar H, Felzel E, Murk AJ, Thain J, Hosoe K, Schoeters G, Legler J, Brouwer B (2004) Intra- and interlaboratory calibration of the DR CALUX® bioassay for the analysis of dioxins and dioxin-like chemicals in sediments. Environ Toxicol Chem 23:2781–2789Google Scholar
  94. 94.
    Colborn T, vom Saal FS, Soto AM (1993) Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect 101:378–384Google Scholar
  95. 95.
    Kavlock RJ, Daston GP, DeRosa C, FennerCrisp P, Gray LE, Kaattari S, Lucier G, Luster M, Mac MJ, Maczka C, Miller R, Moore J, Rolland R, Scott G, Sheehan DM, Sinks T, Tilson HA (1996) Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the US EPA-sponsored workshop. Environ Health Perspect 104:715–740Google Scholar
  96. 96.
    Eltzov E, Kushmaro A, Marks RS (2009) Biosensors for endocrine disruptors. In: Shaw I (eds) Endocrine-disrupting chemicals in food. Woodhead Publishing in Food Science Technology and Nutrition, pp 183–208Google Scholar
  97. 97.
    Svobodova K, Cajthaml T (2010) New in vitro reporter gene bioassays for screening of hormonal active compounds in the environment. Appl Microbiol Biotechnol 88:839–847Google Scholar
  98. 98.
    Pons M, Gagne D, Nicolas JC, Mehtali M (1990) A new cellular model of response to estrogens: a bioluminescent test to characterize (anti)estrogen molecules. Biotechniques 9:450Google Scholar
  99. 99.
    Demirpence E, Duchesne MJ, Badia E, Gagne D, Pons M (1993) MVLN cells—a bioluminescent MCF-7-derived cell line to study the modulation of estrogenic activity. J Steroid Biochem Mol Biol 46:355–364Google Scholar
  100. 100.
    Shue MF, Chen FA, Chen TC (2010) Total estrogenic activity and nonylphenol concentration in the Donggang River. Taiwan. Environ Monit Assess 168:91–101Google Scholar
  101. 101.
    Wang C, Wang T, Liu W, Ruan T, Zhou QF, Liu JY, Zhang AQ, Zhao B, Jiang GB (2012) The in vitro estrogenic activities of polyfluorinated iodine alkanes. Environ Health Perspect 120:119–125Google Scholar
  102. 102.
    Balaguer P, Francois F, Comunale F, Fenet H, Boussioux AM, Pons M, Nicolas JC, Casellas C (1999) Reporter cell lines to study the estrogenic effects of xenoestrogens. Sci Total Environ 233:47–56Google Scholar
  103. 103.
    Witters H, Freyberger A, Smits K, Vangenechten C, Lofink W, Weimer M, Bremer S, Ahr PHJ, Berckmans P (2010) The assessment of estrogenic or anti-estrogenic activity of chemicals by the human stably transfected estrogen sensitive MELN cell line: results of test performance and transferability. Reprod Toxicol 30:60–72Google Scholar
  104. 104.
    Legler J, van den Brink CE, Brouwer A, Murk AJ, van der Saag PT, Vethaak AD, van der Burg B (1999) Development of a stably transfected estrogen receptor-mediated luciferase reporter gene assay in the human T47D breast cancer cell line. Toxicol Sci 48:55–66Google Scholar
  105. 105.
    Wilson VS, Bobseine K, Gray LE (2004) Development and characterization of a cell line that stably expresses an estrogen-responsive luciferase reporter for the detection of estrogen receptor agonist and antagonists. Toxicol Sci 81:69–77Google Scholar
  106. 106.
    Legler J, Zeinstra LM, Schuitemaker F, Lanser PH, Bogerd J, Brouwer A, Vethaak AD, De Voogt P, Murk AJ, Van der Burg B (2002) Comparison of in vivo and in vitro reporter gene assays for short-term screening of estrogenic activity. Environ Sci Technol 36:4410–4415Google Scholar
  107. 107.
    Blankvoort BMG, de Groene EM, van Meeteren-Kreikamp AP, Witkamp RF, Rodenburg RJT, Aarts J (2001) Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor. Anal Biochem 298:93–102Google Scholar
  108. 108.
    Wilson VS, Bobseine K, Lambright CR, Gray LE (2002) A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists. Toxicol Sci 66:69–81Google Scholar
  109. 109.
    Hall RE, Tilley WD, McPhaul MJ, Sutherland RL (1992) Regulation of androgen receptor-gene expression by steroids and retinoic acid in human breast-cancer cells. Int J Cancer 52:778–784Google Scholar
  110. 110.
    Vladusic EA, Hornby AE, Guerra-Vladusic FK, Lakins J, Lupu R (2000) Expression and regulation of estrogen receptor beta in human breast tumors and cell lines. Oncol Rep 7:157–167Google Scholar
  111. 111.
    Aranda A, Pascual A (2001) Nuclear hormone receptors and gene expression. Physiol Rev 81:1269–1304Google Scholar
  112. 112.
    Quaedackers ME, Van den Brink CE, Wissink S, Schreurs R, Gustafsson JA, Van der Saag PT, Van der Burg B (2001) 4-hydroxytamoxifen trans-represses nuclear factor-kappa B activity in human osteoblastic U2-OS cells through estrogen receptor (ER)alpha, and not through ER beta. Endocrinology 142:1156–1166Google Scholar
  113. 113.
    Sonneveld E, Jansen HJ, Riteco JAC, Brouwer A, van der Burg B (2005) Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays. Toxicol Sci 83:136–148Google Scholar
  114. 114.
    van der Burg B, Schreurs R, van der Linden S, Seinen W, Brouwer A, Sonneveld E (2008) Endocrine effects of polycyclic musks: do we smell a rat? Int J Androl 31:188–193Google Scholar
  115. 115.
    Sonneveld E, Riteco JAC, Jansen HJ, Pieterse B, Brouwer A, Schoonen WG, van der Burg B (2006) Comparison of in vitro and in vivo screening models for androgenic and estrogenic activities. Toxicol Sci 89:173–187Google Scholar
  116. 116.
    Leskinen P, Michelini E, Picard D, Karp M, Virta M (2005) Bioluminescent yeast assays for detecting estrogenic and androgenic activity in different matrices. Chemosphere 61:259–266Google Scholar
  117. 117.
    Michelini E, Leskinen P, Virta M, Karp M, Roda A (2005) A new recombinant cell-based bioluminescent assay for sensitive androgen-like compound detection. Biosens Bioelectron 20:2261–2267Google Scholar
  118. 118.
    Sanseverino J, Gupta RK, Layton AC, Patterson SS, Ripp SA, Saidak L, Simpson ML, Schultz TW, Sayler GS (2005) Use of Saccharomyces cerevisiae BLYES expressing bacterial bioluminescence for rapid, sensitive detection of estrogenic compounds. Appl Environ Microbiol 71:4455–4460Google Scholar
  119. 119.
    Eldridge ML, Sanseverino J, Layton AC, Easter JP, Schultz TW, Sayler GS (2007) Saccharomyces cerevisiae BLYAS, a new bioluminescent bioreporter for detection of androgenic compounds. Appl Environ Microbiol 73:6012–6018Google Scholar
  120. 120.
    Sanseverino J, Eldridge ML, Layton AC, Easter JP, Yarbrough J, Schultz TW, Sayler GS (2009) Screening of potentially hormonally active chemicals using bioluminescent yeast bioreporters. Toxicol Sci 107:122–134Google Scholar
  121. 121.
    Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM (2009) Bisphenol-A and the great divide: A review of controversies in the field of endocrine disruption. Endocr Rev 30:75–95Google Scholar
  122. 122.
    Bonefeld-Jorgensen EC, Long MH, Hofmeister MV, Vinggaard AM (2007) Endocrine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review. Environ Health Perspect 115:69–76Google Scholar
  123. 123.
    Mankidy R, Wiseman S, Ma H, Giesy JP (2013) Biological impact of phthalates. Toxicol Lett 217:50–58Google Scholar
  124. 124.
    Preuss TG, Gurer-Orhan H, Meerman J, Ratte HT (2010) Some nonylphenol isomers show antiestrogenic potency in the MVLN cell assay. Toxicol in Vitro 24:129–134Google Scholar
  125. 125.
    Schiliro T, Porfido A, Spina F, Varese GC, Gilli G (2012) Oestrogenic activity of a textile industrial wastewater treatment plant effluent evaluated by the E-screen test and MELN gene-reporter luciferase assay. Sci Total Environ 432:389–395Google Scholar
  126. 126.
    He YH, Wiseman SB, Hecker M, Zhang XW, Wang N, Perez LA, Jones PD, El-Din MG, Martin JW, Giesy JP (2011) Effect of ozonation on the estrogenicity and androgenicity of oil sands process-affected water. Environ Sci Technol 45:6268–6274Google Scholar
  127. 127.
    Pereira RO, Postigo C, de Alda ML, Daniel LA, Barcelo D (2011) Removal of estrogens through water disinfection processes and formation of by-products. Chemosphere 82:789–799Google Scholar
  128. 128.
    Kortenkamp A (2007) Ten years of mixing cocktails: a review of combination effects of endocrine-disrupting chemicals. Environ Health Perspect 115:98–105Google Scholar
  129. 129.
    Fenet H, Gomez E, Pillon A, Rosain D, Nicolas JC, Casellas C, Balaguer P (2003) Estrogenic activity in water and sediments of a French river: contribution of alkylphenols. Arch Environ Contam Toxicol 44:1–6Google Scholar
  130. 130.
    Close DM, Patterson SS, Ripp SA, Baek SJ, Sanseverino J, Sayler GS (2010) Autonomous bioluminescent expression of the bacterial luciferase gene cassette (lux) in a mammalian cell line. PLoS ONE 5:e12441Google Scholar
  131. 131.
    Bundy JG, Campbell CD, Paton GI (2001) Comparison of response of six different luminescent bacterial bioassays to bioremediation of five contrasting oils. J Environ Monit 3:404–410Google Scholar
  132. 132.
    Diplock EE, Mardlin DP, Killham KS, Paton GI (2009) Predicting bioremediation of hydrocarbons: Laboratory to field scale. Environ Pollut 157:1831–1840Google Scholar
  133. 133.
    Werlen C, Jaspers MCM, van der Meer JR (2004) Measurement of biologically available naphthalene in gas and aqueous phases by use of a Pseudomonas putida biosensor. Appl Environ Microbiol 70:43–51Google Scholar
  134. 134.
    Paton GI, Reid BJ, Sempled KT (2009) Application of a luminescence-based biosensor for assessing naphthalene biodegradation in soils from a manufactured gas plant. Environ Pollut 157:1643–1648Google Scholar
  135. 135.
    Kapanen A, Vikman M, Rajasärkkä J, Virta M, Itävaara M (2013) Biotests for environmental quality assessment of composted sewage sludge. Waste Manag 33:1451–1460Google Scholar
  136. 136.
    Sakai S, Takigami H (2003) Integrated biomonitoring of dioxin-like compounds for waste management and environment. Ind Health 41:205–214Google Scholar
  137. 137.
    Hilscherova K, Dusek L, Sidlova T, Jalova V, Cupr P, Giesy JP, Nehyba S, Jarkovsky J, Klanova J, Holoubek I (2010) Seasonally and regionally determined indication potential of bioassays in contaminated river sediments. Environ Toxicol Chem 29:522–534Google Scholar
  138. 138.
    Kanematsu M, Hayashi A, Denison MS, Young TM (2009) Characterization and potential environmental risks of leachate from shredded rubber mulches. Chemosphere 76:952–958Google Scholar
  139. 139.
    Richter CA, Tieber VL, Denison MS, Giesy JP (1997) An in vitro rainbow trout cell bioassay for aryl hydrocarbon receptor-mediated toxins. Environ Toxicol Chem 16:543–550Google Scholar
  140. 140.
    Hahn ME (2002) Biomarkers and bioassays for detecting dioxin-like compounds in the marine environment. Sci Total Environ 289:49–69Google Scholar
  141. 141.
    Yang J-H, Lee H-G, Park K-Y (2008) Development of human dermal epithelial cell-based bioassay for the dioxins. Chemosphere 72:1188–1192Google Scholar
  142. 142.
    He G, Tsutsumi T, Zhao B, Baston DS, Zhao J, Heath-Pagliuso S, Denison MS (2011) Third-generation Ah receptor–responsive luciferase reporter plasmids: Amplification of dioxin-responsive elements dramatically increases CALUX bioassay sensitivity and responsiveness. Toxicol Sci 123:511–522Google Scholar
  143. 143.
    Bergamasco AMD, Eldridge M, Sanseverino J, Sodre FF, Montagner CC, Pescara IC, Jardim WF, Umbuzeiro GD (2011) Bioluminescent yeast estrogen assay (BLYES) as a sensitive tool to monitor surface and drinking water for estrogenicity. J Environ Monit 13:3288–3293Google Scholar
  144. 144.
    Jardim WF, Montagner CC, Pescara IC, Umbuzeiro GA, Bergamasco AMD, Eldridge ML, Sodre FF (2012) An integrated approach to evaluate emerging contaminants in drinking water. Sep Purif Technol 84:3–8Google Scholar
  145. 145.
    Salste L, Leskinen P, Virta M, Kronberg L (2007) Determination of estrogens and estrogenic activity in wastewater effluent by chemical analysis and the bioluminescent yeast assay. Sci Total Environ 378:343–351Google Scholar
  146. 146.
    Furuichi T, Kannan K, Suzuki K, Tanaka S, Giesy JP, Masunaga S (2006) Occurrence of estrogenic compounds in and removal by a swine farm waste treatment plant. Environ Sci Technol 40:7896–7902Google Scholar
  147. 147.
    Mahjoub O, Escande A, Rosain D, Casellas C, Gomez E, Fenet H (2011) Estrogen-like and dioxin-like organic contaminants in reclaimed wastewater: transfer to irrigated soil and groundwater. Water Sci Technol 63:1657–1662Google Scholar
  148. 148.
    David A, Gomez E, Ait-Aissa S, Rosain D, Casellas C, Fenet H (2010) Impact of urban wastewater discharges on the sediments of a small Mediterranean river and associated coastal environment: Assessment of estrogenic and dioxin-like activities. Arch Environ Contam Toxicol 58:562–575Google Scholar
  149. 149.
    Mnif W, Zidi I, Hassine AIH, Gomez E, Bartegi A, Roig B, Balaguer P (2012) Monitoring endocrine disrupter compounds in the Tunisian Hamdoun River using in vitro bioassays. Soil Sediment Contam 21:815–830Google Scholar
  150. 150.
    Maletz S, Floehr T, Beier S, Klumper C, Brouwer A, Behnisch P, Higley E, Giesy JP, Hecker M, Gebhardt W, Linnemann V, Pinnekamp J, Hollert H (2013) In vitro characterization of the effectiveness of enhanced sewage treatment processes to eliminate endocrine activity of hospital effluents. Water Res 47:1545–1557Google Scholar
  151. 151.
    Vethaak AD, Lahr J, Schrap SM, Belfroid AC, Rijs GBJ, Gerritsen A, de Boer J, Bulder AS, Grinwis GCM, Kuiper RV, Legler J, Murk TAJ, Peijnenburg W, Verhaar HJM, de Voogt P (2005) An integrated assessment of estrogenic contamination and biological effects in the aquatic environment of The Netherlands. Chemosphere 59:511–524Google Scholar
  152. 152.
    Houtman CJ, Booij P, van der Valk KM, van Bodegom PM, van den Ende F, Gerritsen AAM, Lamoree MH, Legler J, Brouwer A (2007) Biomonitoring of estrogenic exposure and identification of responsible compounds in bream from Dutch surface waters. Environ Toxicol Chem 26:898–907Google Scholar
  153. 153.
    Leusch FDL, De Jager C, Levi Y, Lim R, Puijker L, Sacher F, Tremblay LA, Wilson VS, Chapman HF (2010) Comparison of five in vitro bioassays to measure estrogenic activity in environmental waters. Environ Sci Technol 44:3853–3860Google Scholar
  154. 154.
    Wehmas LC, Cavallin JE, Durhan EJ, Kahl MD, Martinovic D, Mayasich J, Tuominen T, Villeneuve DL, Ankley GT (2011) Screening complex effluents for estrogenic activity with the T47D-KBluc cell bioassay: assay optimization and comparison with in vivo responses in fish. Environ Toxicol Chem 30:439–445Google Scholar
  155. 155.
    Maggioni S, Balaguer P, Chiozzotto C, Benfenati E (2013) Screening of endocrine-disrupting phenols, herbicides, steroid estrogens, and estrogenicity in drinking water from the waterworks of 35 Italian cities and from PET-bottled mineral water. Environ Sci Pollut Res 20:1649–1660Google Scholar
  156. 156.
    Suzuki G, Tue NM, Malarvannan G, Sudaryanto A, Takahashi S, Tanabe S, Sakai S, Brouwer A, Uramaru N, Kitamura S, Taldgami H (2013) Similarities in the endocrine-disrupting potencies of indoor dust and flame retardants by using human osteosarcoma (U2OS) cell-based reporter gene assays. Environ Sci Technol 47:2898–2908Google Scholar
  157. 157.
    Van der Linden SC, Heringa MB, Man HY, Sonneveld E, Puijker LM, Brouwer A, Van der Burg B (2008) Detection of multiple hormonal activities in wastewater effluents and surface water, using a panel of steroid receptor CALUX bioassays. Environ Sci Technol 42:5814–5820Google Scholar
  158. 158.
    Blankvoort BMG, Rodenburg RJT, Murk AJ, Koeman JH, Schilt R, Aarts J (2005) Androgenic activity in surface water samples detected using the AR-LUX assay: indications for mixture effects. Environ Toxicol Pharmacol 19:263–272Google Scholar
  159. 159.
    Bellet V, Hernandez-Raquet G, Dagnino S, Seree L, Pardon P, Bancon-Montiny C, Fenet H, Creusot N, Ait-Aissa S, Cavailles V, Budzinski H, Antignac JP, Balaguer P (2012) Occurrence of androgens in sewage treatment plants influents is associated with antagonist activities on other steroid receptors. Water Res 46:1912–1922Google Scholar
  160. 160.
    Schriks M, van Leerdam JA, van der Linden SC, van der Burg B, van Wezel AP, de Voogt P (2010) High-resolution mass spectrometric identification and quantification of glucocorticoid compounds in various wastewaters in The Netherlands. Environ Sci Technol 44:4766–4774Google Scholar
  161. 161.
    Jugan ML, Levy-Bimbot M, Pomerance M, Tamisier-Karolak S, Blondeau JP, Levi Y (2007) A new bioluminescent cellular assay to measure the transcriptional effects of chemicals that modulate the alpha-1 thyroid hormone receptor. Toxicol in Vitro 21:1197–1205Google Scholar
  162. 162.
    Jugan ML, Oziol L, Bimbot M, Huteau V, Tamisier-Karolak S, Blondeau JP, Levi Y (2009) In vitro assessment of thyroid and estrogenic endocrine disruptors in wastewater treatment plants, rivers and drinking water supplies in the greater Paris area (France). Sci Total Environ 407:3579–3587Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Tingting Xu
    • 1
  • Dan Close
    • 2
  • Abby Smartt
    • 3
    • 4
  • Steven Ripp
    • 3
    • 4
  • Gary Sayler
    • 1
    • 3
    • 4
  1. 1.Joint Institute for Biological SciencesThe University of TennesseeKnoxvilleUSA
  2. 2.Biosciences DivisionOak Ridge National LaboratoryOak RidgeUSA
  3. 3.Center for Environmental BiotechnologyThe University of TennesseeKnoxvilleUSA
  4. 4.Department of MicrobiologyThe University of TennesseeKnoxvilleUSA

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