Abstract
In vitro cell bioassays are useful techniques for the determination of receptor-mediated activities in environmental samples containing complex mixtures of contaminants. The cell bioassays determine contamination by pollutants that act through specific modes of action. This article presents strategies for the evaluation of aryl hydrocarbon receptor (AhR)-(hereafter referred as dioxin-like) or estrogen receptor (ER)-mediated activities of potential endocrine disrupting compounds (EDCs) in complex environmental mixtures. Extracts from various types of environmental or food matrices can be tested by this technique to evaluate their 2,3,7,8-tetrachlorodibenzop-dioxin equivalents (TCDD-EQs) or estrogenic equivalents (E2-EQs) and to identify contaminated samples that need further investigation using resource-intensive instrumental analyses. Fractionation of sample extracts exhibiting significant activities, and subsequent reanalysis with the bioassays can identify important classes of contaminants that are responsible for the observed activity. Effect-directed chemical analysis is performed only for the active fractions to determine the responsible compounds. Mass-balance estimates of all major compounds contributing to the observed effects can be calculated to determine if all of the activity has been identified, and to assess the potential for interactions such as synergism or antagonism among contaminants present in the complex mixtures. The bioassay approach is an efficient (fast and cost effective) screening system to identify the samples of interest and to provide basic information for further analysis and risk evaluation.
Similar content being viewed by others
References
Gray, L.E.; Kelce, W.; Wiese, T.; Tyl, R.; Gaido, K.; Cook, J.; Klinefelter, G.; Desaulniers, D.; Wilson, E.; Zacharewski, T.; Waller, C.; Foster, P.; Laskey, J.; Reel, J.; Giesy, J.; Laws, S.; McLachlan, J.; Breslin, W.; Cooper, R.; Di Guilio, R.; Johnson, R.; Purdy, R.; Mihaich, E.; Safe, S.; Sonnenschein, G.; Welshons, W.; Miller, R.; McMaster, S., Colborn, T. (1997): Endocrine Screening Methods Workshop Report: Detection of Estrogenic and Androgenic Hormonal and Antihormonal Activity for Chemicals That Act Via Receptor or Steroidogenic Enzyme Mechanisms. Reproduct. Toxicol. 11, 719–750
Gillesby, B.E.; Zacharewski, T.R. (1998): Exoestrogens: Mechanisms of Action and Strategies for Identification and Assessment, Environ. Toxicol. Chem. 17, 3–14
Ankley, G.; Mihaich, E.; Stahl, R.; Tillit, D.E.; Colborn, T.; McMaster, S.; Miller, R.; Bantle, J.; Campbell, P.; Denslow, N.; Dickerson, R.; Folmar, L.; Fry, M.; Giesy, J.; Gray, L.E.; Guiney, P.; Hutchinson, T.; Kennedy, S.; Kramer, V.; Leblanc, G.; Mayes, M.; Nimrod, A.; Patino, R.; Peterson, R.; Purdy, R.; Ringer, R.; Thomas, P.; Touart, L.; Van der Kraak, G.; Zacharewski, T. (1998): Overview of a Workshop on Screening Methods for Detecting Potential (Anti-) Estrogenic/Androgenic Chemicals in Wildlife, Environ. Toxicol. Chem. 17, 68–87
Van den Berg, M.; Birnbaum, L.; Bosveld, B.T.C.; Brunstrom, B.; Cook, P.; Feeley, M.; Giesy, J.P.; Hanberg, A.; Hasegawa, R.; Kennedy, S.; Kubiak, T.; Larsen, J.C.; Van Leeuwen, F.X.R.; Djien Liem, A.K.; Nolt, C.; Peterson, R. E.; Poellinger, L.; Safe, S.; Schrenk, D.; Tillitt, D.E.; Tysklind, M.; Younes, M.; Waern, F.; Zacharewski, T. (1998): Toxic Equivalency Factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environ. Health Perspect. 106, 775–790
Ahlborg, U.G.; Brouwer, A.; Fingerhut, M. A.; Jacobson, J.L.; Jacobson, S.W.; Kennedy, S.W.; Kettrup, A.A.F.; Koeman, J.H.; Poiger, H.; Rappe, C.; Safe, S.; Seegal, R.F.; Tuomisto, J.; Van den Berg, M. (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. European J. Pharmacol. 228, 179–199
Peterson, R.E.; Theobald, H.M.; Kimmel, G.L. (1993): Developmental and Reproductive Toxicity of Dioxins and Related Compounds: Cross-Species Comparisons. Crit. Rev. Toxicol. 23, 283–335
Nebert, D.W.; Puga, A.; Vasiuou, V. (1993): Role of the Ah Receptor and the Dioxin-Inducible [Ah] Gene Battery in Toxicity, Cancer, and Signal Transduction. Ann. New York Acad. Sci.; 625–641
Lucier, G.W.; Portier, CH.J.; Gallo, M.A. (1993): Receptor Mechanism and Dose-Response Models for the Effects of Dioxins. Environ. Health Perspect. 1, 36–44
Zacharewski, T.R.; Berhane, K.; Gilleby, B.E.; Burnison, B.K. (1995): Detection of Estrogen- and Dioxin-like Activity in Pulp and Paper Mill Black Liquor and Effluent Using in vitro Recombinant Receptor/Reporter Gene Assays. Environ. Sci. Technol. 29, 2140–2146
Safe, S.H. (1995): Modulation of Gene Expression and Endocrine Response Pathways by 2,3,7,8-tetrachloridobenzo-p-dioxin and Related Compounds. Pharmac. Ther. 2, 247–281.
Denison, M.S.; Heath-Pagliuso, S. (1998): The Ah Receptor: A Regulator of the Biochemical and Toxicological Actions of Structurally Diverse Chemicals. Bull. Environ. Contam. Toxicol. 61, 557–568
Hankinson, O. (1995): The Aryl Hydrocarbon Receptor Complex. Ann. Rev. Pharmacol. Toxicol. 35, 307–340
Poland, A.; Knutson, J.C. (1982): 2,3,7,8-tetrachlorodibenzo-p-dioxin and Related Halogenated Aromatic Hydrocarbons: Examination of the Mechanism of Toxicity. Ann. Rev. Pharmacol. Toxicol. 22, 517–554
Lewis, D.F.V.; Ioannides, C., Parke, D.V. (1986): Molecular dimensions of the substrate binding site of cytochrome P-448. Biochem. Pharmacol. 35, 2179–2185
Blankenship, A.; Kannan, K.; Villalobos, S.; Villeneuve, D.; Faladysz, J.; Imagawa, T.; Jakobsson, E.; Giesy, J. (2000): Relative Potencies of Halowax Mixtures and Individual Polychlorinated Napthalenes (PCNs) to induce Ah Receptor Mediated Responses in the Rat Hepatoma H4IIE-luc Cell Bioassay. Environ. Sci. & Technol. (In press)
Till, M.; Behnisch, P.; Hagenmaier, H.; Bock, K.W.; Schrenk, D. (1997): Dioxin-like Components in Incinerator Fly Ash: A Comparison between Chemical Analysis Data and Results from a Cell Culture Bioassay. Environ. Health Perspect. 105, 1326–1332
Van den Heuvel, M.R.; Munkittrick, K. R.; Van der Kraak, G.J.; McMaaster, M.E.; Portt, C.B.; Servos, M.R.; Dixon, D. J. (1994): Survey of Receiving-Water Environmental Impacts Associated with Discharges from Pulp Mills. 4. Bioassay-derived 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxic Equivalent Concentration in White Sucker in Relation to Biochemical Indicators of Impact. Environ. Toxicol. Chem. 13, 1117–1126
Sanderrson, J.T.; Giesy, J.P. (1998): Wildlife Toxicology, Functional Response Assays. In: Meyers, R.A. (ed.) Encyclopedia of Environmental Analysis and Remediation, John Wiley & Sons, Inc.; USA, 5272–5297
Sohoni, P.; Soto, J.P. (1998): Several Environmental Oestrogens Are Also Antiandrogens, J. Endocrinol. 158, 327–339
Machala, M.; Vondracek, J. (1998): Estrogenic Activity of Xenobiotics. Vet. Med.-Czech 10, 311–317
Joyeux, A.; Balaguer, P.; Germain, P.; Boussioux, A.M.; Pons, M.; Nicolas, J.C. (1997): Engineered Cell Lines as a Tool for Monitoring Biological Activity of Hormone Analogs. Anal. Biochem. 249, 119–130
Fielden, M.R.; Chen, I.; Chtttim, B.; Safe, S.H.; Zacharewski, T.R. (1997): Examination of the Estrogenicity of 2,4,6,2’,6’-Pentachlorobiphenyl (PCB 104), Its Hydroxylated Metabolite 2,4,6,2’,6’-Pentachloro-4-biphenylol (OH-PCB 104), and Further Chlorinated Derivative 2,4,6,2’,4’,6’-Hexachlorobiphenyl (PCB 155). Environ. Health Perspect. 105, 1238–1248.
Villeneuve, D.; Blankenship, A.L.; Giesy, J.P. (1998): Interactions Between Environmental Xenobiotics and Estrogen Receptor-Mediated Responses In: Denison, M.S.; Helferich, W.G. (eds.) Toxicant-receptor interactions. Taylor and Francis, Philadelphia, PA, USA, 69–99
Gaido, K.W.; McDonnel, D.P.; Korach, K.S.; Safe, S.H. (1997): Estrogenic Activity of Chemical Mixtures: Is there Synergism? CUT Activities, Chemical Industry Institute of Toxicology 2, 1–7
Stahlschmidt-Allner, P.; Allner, B.; Rombke, J.; Knacker, T. (1997): Endocrine Disrupters in the Aquatic Environment. Environ. Sci. Pollut. Res. 4, 155–162
Markiewicz, L.; Garey, J.; Adlercreutz, H.; Gurpide, E. (1993): In vitro Bioassays of Non-steroidal Phytoestrogens. Steroid Biochem. Molec. Biol. 45, 399–405
Wang, C.; Makela, T.; Hase, T.; Adlercreutz, H.; Kurzer, M.S. (1994): Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. J. Steroid Biochem.Mol.Biol. 50, 205–212
Legler, J.; Van den Brink, C.; Brower, A.; Vethaak, D.; Van der Saag, P.; Murk, T.; Van der Burg, B. (1998): Assessment of (Anti)estrogenic compounds using a Stably Transfected Luciferase Reporter Gene Assay in the Human T47-D Breast Cancer Cell Line. Organohalogen Compounds 37, 265–268
Nimrod, A.C.; Benson, W.H. (1997): Xenobiotic interaction with and alteration of channel catfish estrogen receptor. Toxicol. Appl. Pharmacol. 147, 381–390
Kuiper, G.G.; Lemmen, J.G.; Carlsson, B.; Corton, J.C.; Safe, S.H.; Van der Saag, P.T.; Van der Burg, B.; Gustafsson, J.A. (1998): Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinol. 139, 10, 4252–4263
Safe, S.; Gaido, K. (1998): Phytoestrogens and Anthropogenic Estrogenic Compounds. Environ. Toxicol. Chem. 17, 119–126
Le Bail, J.C.; Varnat, F.; Nicolas, J.C.; Habrioux, G. (1998): Estrogenic and Antiproliferative Activities on MCF-7 Human Breast Cancer Cells by Flavonoids. Cancer Lett. 130, 209–216
Celius, T.; Haugen, T.B.; Grotmol, T. Walther, B.T. (1999): A sensitive zonagenetic assay for rapid in vitro assessment of estrogenic potency of xenobiotics and mycotoxins. Environ. Health Perspect. 107, 63–68
Taylor, C.M.; Blanchard, B.; Zava, D.T. (1984): Estrogen receptor-mediated and cytotoxic effects of the antiestrogens tamoxifen and 4-hydroxytamoxifen. Cancer-Res. 44, 1409–1414
Ramkumart, T.; Adler, S. (1995): Differential positive and negative transcriptional regulation by tamoxifen. Endocrinol. 136, 536–542
Shelby, M.D.; Newbold, R.R.; Tully, D.B.; Chae, K.; Davis, V.L. (1996): Assessing Environmental Chemicals for Estrogenicity Using a Combination of In vitro and In vivo Assays. Environ. Health Perspect. 104, 1296–1300
Favoni, R.E.; De Cupis, A. (1998): Steroidal and Nonsteroidal Oestrogen Antagonists in Breast Cancer: Basic Clin. Appr.; TiPS 19, 406–415
Routledge, E.J.; Parker, J.; Odum, J.; Ashby, J.; Sumpter, J.P. (1998): Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic. Toxicol. Appl. Pharmacol. 153, 12–19
Soto, A.M.; Sonnenschein, C.; Chung, K.L.; Fernandez, M.F.; Olea, N.; Serrano, F.O. (1995): The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ. Health Perspect. 103, Suppl 7, 113–122
Sumpter, J.P.; Jobling, S. (1995): Vitellogenesis as a Biomarker for Estrogenic Contamination of the Aquatic Environment. Environ. Health Perspect. 103, Suppl.7, 173–178
Kelce, W.R.; Stone, C.R.; Laws, S.C.; Gray, L.E.; Kemppainen, J.A.; Wilson, E.M. (1995): Persistent DDT metabolite p,p′- DDE is a potent androgen receptor antagonist. Nature 375, 581–585
Klotz, D.M.; Beckman, B.S.; Hill, S.M.; McLachlan, J.A.; Walters, M.R.; Arnold, S.F. (1996): Identification of environmental chemicals with estrogenic activity using a combination of in vitro assays. Environ. Health Perspect. 104, 10, 1084–1089
Soto, A.M.; Chung, K.L.; Sonnenschein, C. (1994): The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. Environ. Health Perspect. 102, 380–383
Petit, F.; Le-Goff, P.; Cravedi, J.P.; Valotaire, Y.; Pakdel, F. (1997): Two complementary bioassays for screening the estrogenic potency of xenobiotics: recombinant yeast for trout estrogen receptor and trout hepatocyte cultures. J. Mol. Endocrinol. 19, 321–335
Asmathbanu, I.; Kaliwal, B.B. (1997): Temporal effect of methyl parathion on ovarian compensatory hypertrophy, follicular dynamics and estrous cycle in hemicastrated albino rats. J. Basic Clin. Physiol. Pharmacol. 8, 237–254
Cranmer, J.M.; Cranmer, M.F.; Goad, P.T. (1984): Prenatal chlordane exposure: effects on plasma corticosterone concentrations over the lifespan of mice. Environ.Res. 35, 204–210
Go, V.; Garey, J.; Wolff, M.S.; Pogo, B.G.T. (1999): Estrogenic Potential of Certain Pyrethroid Compounds in the MCF-7 Human Breast Carcinoma Cell Line, Environ. Health Perspect. 107, 173–177
Kelce, W.R.; Monosson, E.; Gamscsik, M.P.; Laws, S.C.; Gray, L.E. (1994): Environmental Hormone Disruptors: Evidence That Vinclozolin Developmental Toxicity is Mediated by Antiandrogenic Metabolites. Toxicol. App. Pharmacol. 126, 267–285
Tennant, M.K.; Hill, D.S.; Eldridge, J.C.; Wetzel, L.T.; Breckenridge, C.B.; Stevens, J.T. (1994): Possible antiestrogenic properties of chloro-s-triazines in rat uterus. J. Toxicol. Environ. Health 43, 183–196
Matthiessen, P.; Gibbs, P.E. (1998): Critical Appraisal of the Evidence for Tributyltin-mediated Endocrine Disruption in Mollusks. Environ. Toxicol. Chem. 17, 37–43
Jobling, S.; Reynolds, T.; White, R.; Parker, M.G.; Sumpter, J.P. (1995): A Variety of Environmental Persistant Chemicals, Including Some Phtalate Plasticizers, Are Weakly Estrogenic. Environ. Health Perspect. 103, 582–587
Servos, M.R. (1999): Review of the Aquatic Toxicity, Estrogenic Responses and Bioaccumulation of Alkylphenols and Alkylphenol Polyethoxylates. Water Qual.Res.J.Canada 34, 123 -177
Beard, A.P.; Bartlewski, P.M.; Rawlings, N.C. (1999): Endocrine and reproductive function in ewes exposed to the organochlorine pesticides lindane or pentachlorophenol. J. Toxicol. Environ. Health. 56, 23–46
Safe, S.; Krishnan, V. (1995): Cellular and Molecular Biology of Aryl Hydrocarbon (Ah) Receptor — Mediated Gene Expression. Arch. Toxicol.; Suppl. 17, 99 -115
Matta, M.B.; Cairncross, C.; Kocan, R.M. (1998): Possible Effects of Polychlorinated Biphenyls on Sex Determination in Rainbow Trout. Environ. Toxicol. Chem. 17, 26–29
Kramer, V.J.; Helferich, W.G.; Bergman, A.; Klasson-Wehler, E.; Giesy, J.P. (1997): Hydroxylated Polychlorinated Biphenyl Metabolites are Anti-estrogenic in a Stably Transfected Human Breast Adenocarcinoma (MCF7) Cell Line. Toxicol. App. Pharmacol. 144, 363–376
Tran, D.Q.; Ide, C.F.; McLachlan, J.A.; Arnold, S.F.(1996): The Anti-estrogenic Activity of Selected Polynuclear Aromatic hydrocarbons in Yeast Expressing Human Estrogen Receptor. Biochem.Biophys.Res.Comm. 229, 102–108
Chaloupka, K.; Krishnan, V.; Safe, S. (1992): Polynuclear Aromatic Hydrocarbon Carcinogens as Antiestrogens in MCF-7 Human Breast Cancer Cells: Role of the Ah Receptor Carcinogenesis 12, 2233–2239
Santodonato, J. (1997): Review of the Estrogenic and Antiestrogenic Activity of Polycyclic Aromatic Hydrocarbons: Relationship to Carcinogenicity. Chemosphere 34, 835–848
Clemons, J. H.; Allan, L.M.; Marvin, C.H.; Wu, Z.; McCarry, B.E.; Bryant, D.W.; Zacharewski, T.R. (1998): Evidence of Estrogen- and TCDD-Like Activities in Crude and Fractionated Extracts of PM10 Air Particulate Material Using In Vitro Gene Expression Assay. Environ. Sci. Technol. 32, 1853–1860
Laskey, J.W.; Phelps, P. V. (1991): Effect of Cadmium and Other Metal Cations on in Vitro Leydig Cell Testosterone Production. Toxicol. Appl. Pharmacol. 108, 296–306
Ricard, A.C.; Daniel, C.; Anderson, P.; Hontela, A. (1998): Effects of Subchronic Exposure to Cadmium Chloride on Endocrine and Metabolic Functions in Rainbow Trout Oncorhynchus mykiss. Arch.Environ.Contam.Toxicol. 34, 377–381
Lafuente, A.; Blanco, A.; Marquez, N.; Alvarez-Demanuel, E.; Esquifino, A.I. (1997): Effects of Acute and Subchronic Cadmium Administration on Pituitary Hormone Secretion in Rat. Rev. Esp. Fisiol. 53, 265–269
Ronis, M.J.; Gandy, J.; Badger, T. (1998): Endocrine mechanisms underlying reproductive toxicity in the developing rat chronically exposed to dietary lead. J.Toxicol. Environ. Health 54, 77–99
Tillitt, D.E.; Ankley, G.T.; Verbrugge, D.A.; Giesy, J.P.; Ludwig, J.P.; Kubiak, T.J. (1991): H4IIE Rat Hepatoma Cell Bioassay-Derived 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Equivalents in Colonial Fish-Eating Waterbird Eggs from the Great Lakes. Arch. Environ. Contam. Toxicology 21, 91–101
Hahn, M.E.; Woodward, B.L.; Stegeman, J.J.; Kennedy, S.W. (1996): Rapid Assessment of Induced Cytochrome P4501A Protein and Catalytic Activity in Fish Hepatoma Cells Grown in Multiwell Plates: Response to TCDD, TCDF, and Two Planar PCBs. Environ. Toxicol. Chem. 4, 582–591
Pelissero, C.; Flouriot, G.; Foucher, J.L.; Bennetau, B.; Dunogues, J.; Le Gac, F.; Sumpter, J.P. (1993): Vitellogenin Synthesis in Cultured Hepatocytes — an In vitro Test for the Estrogenic Potency of Chemicals. J.Steroid Biochem. Molec. Biol. 44, 263–272
Zacharewski, T.R. (1997): In Vitro Bioassays for Assessing Estrogenic Substances. Environ. Sci. Technol. 31, 613–623
Garrison, P.M.; Tullis, K.; Aarts, J.M.M.J.G.; Brouwer, A.; Giesy, J.P.; Denison, M.S. (1996): Species-Specific Recombinant Cell Lines as Bioassay Systems for the Detection of 2,3,7,8-tetrachloridobenzo-p-dioxin-like Chemicals. Fund. Appl. Toxicol. 30, 194–203
Willet, K.L.; Gardinali, P.R.; Sericano, J.L.; Wade, T.L.; Safe, S.H. (1997): Characterization of the H411E Rat Hepatoma Cell Bioassay for Evaluation of Environmental Samples Containing Polynuclear Aromatic Hydrocarbons (PAHs). Arch. Environ. Contam. Toxicol. 32, 442–448
Sanderson, J.T.; Aarts J.; M.M.J.G.; Brouwer, A.; Froese, K.L.; Denison, M.S.; Giesy, J.P. (1996): Comparison of Ah Receptor-Mediated Luciferase and Ethoxyresorufin-O-deethylase Induction in H411E Cells: Implications for Their Use as Bioanalytical Tools for Detection of Polyhalogenated Aromatic Hydrocarbons. Toxicol. App. Pharmacol. 137, 316–325
Murk, A.J.; Legler, J.; Denson, M.S.; Giesy, J.P.; van de Guchte, 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. Fund. Appl. Toxicol. 33, 149–60
Kennedy, S.W.; Lorenzen, A.; Jones, S.P.; Hahn, M.E.; Stegeman, J.J. (1996): Cytochrome P4501A Induction in Avian Hepatocyte Cultures: A Promising Approach for Predicting the Sensitivity of Avian Species to Toxic Effects of Halogenated Aromatic Hydrocarbons. Toxicol. App. Pharmacol. 141, 214–230
Kennedy, S.W.; Lorenzen, A.; Norstrom, R.J. (1996): Chicken Embryo Hepatocyte Bioassay for Measuring Cytochrome P4501A-Based 2,3,7,8-tetrachlorodibenzo-p-dioxin Equivalent Concentrations in Environmental Samples. Environ. Sci. Technol. 30, 706–715
Till, M.; Behnisch, P.; Hagenmaier, H.; Bock, K.W.; Schrenk, D. (1997): Dioxin-like Components in Incinerator Fly Ash: A Comparison between Chemical Analysis Data and Results from a Cell Culture Bioassay. Environ. Health Perspect. 105, 1326–1332
El-Fouly, M.H.; Richter, C.A.; Giesy, J.P.; Denison, M.S. (1994): Production of a Novel Recombinant Cell Line for Use as a Bioassay System for Detection of 2,3,7,8-tetrachloridobenzo-p-dioxin-like Chemicals. Environ. Toxicol. Chem. 10, 1581–1588
Clemons, J.H.; Dixon, D.J.; Bols, N.C. (1997): Derivation of 2,3,7,8-TCDD Toxic Equivalent Factors (TEFs) for Selected Dioxins, Furans and PCBs with Rainbow Trout and Rat Liver Cell Lines and the Influence of Exposure Time. Chemosphere 34, 1105–1119
Richter, C.A.; Tieber, V.L.; Denison, M.S.; Giesy, J.P. (1997): An In Vitro Rainbow Trout Cell Bioassay for Aryl Hydrocarbon Receptor-Mediated Toxins. Environ. Toxicol. Chem. 3, 543–550
Anderson, J.W.; Zeng, E.Y.; Jones, J.M. (1999): Correlation between Response of Human Cell Line and Distribution of Sediment Polycyclic Aromatic Hydrocarbons and Polychlorinated Biphenyls on Palos Verdes Shelf, California, USA. Environ. Toxicol. Chem. 18, 1506–1510
Navas, J.M.; Segner, H. (1998): Antiestrogenic Activity of Anthropogenic and Natural Chemicals. Environ. Sci. Pollut. Res. 5, 75–82
Kharat, I.; Saatcioglu, F. (1996): Antiestrogenic Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Are Mediated by Direct Transcriptional Interference with the Liganded Estrogen Receptor. J. Biol. Chem. 271, 10533–10537
Nakama, A.; Yoshikura, T.; Fukunaga, I. (1997): Induction of Cytochrome P450 in HepG2 Cells and Mutagenicity of Extracts of Sediments from a Waste Disposal Site Near Osaka, Japan. Bull. Environ. Contam. Toxicol. 59, 344–351
Villeneuve, D.; Crunkilton, R.L.; Devita, W.M. (1997): Aryl Hydrocarbon Receptor-Mediated Toxic Potency of Dissolved Lipophilic Organic Contaminants Collected from Lincoln Creek, Milwaukee, Wisconsin, USA, to PLHC-1 (Poeciliopsis Lucida) Fish Hepatoma Cells. Environ. Toxicol. Chem. 16, 977–984
Balaguer, P.; Joyeux, A.; Denison, M.S.; Vincent, R.; Gillesby, B.E.; Zacharewski, T.R. (1996): Assessing the Estrogenic and Dioxin-like Activities of Chemicals and Complex Mixtures Using in Vitro Recombinant Receptor-Reporter Gene Assay. Can. J. Physiol. Pharmacol. 74, 216–222
Pons, M.; Gagne, D.; Nicolas, J.C.; Mehtali, M. (1990): A new cellular model of response to estrogens: a bioluminescent test to characterize (anti) estrogen molecules. Biotechniques 9, 450–459
Koistinen, J.; Soimasuo, M.; Tukia, K.; Oikari, A.; Blankenship, A.; Giesy, J.P. (1998): Induction of EROD Activity in Hepa-1 Mouse Hepatoma Cells and Estrogenicity in MCF-7 Human Breast Cancer Cells by Extracts of Pulp Mill Effluents, Sludge, and Sediments Exposed to Effluents. Environ. Toxicol. Chem. 17, 1499–1507
Engwall, M.; Broman, D.; Dencker, L.; Naf, C.; Zebuhr, Y.; Brunstrom, B. (1997): Toxic Potencies of Extracts from Sediments and Settling Particulate Matter Collected in the Recipient of a Bleached Pulp Mill Effluent before and after Abandoning Chlorine Bleaching. Environ. Toxicol. Chem. 16, 1187–1194
Brunstrom, B.; Broman, D.; Dencker, L.; Naf, C.; Vejlens, E.; Zebuhr, Y. (1992): Extracts from Settling Particulate Matter Collected in the Stockholm Archipelago Waters: Embryolethality, Immunotoxicity and EROD, inducing Potency of Fractions Containing Aliphatics/Monoaromatics, Diaromatics or Polyaromatics. Environ. Toxicol. Chem. 11, 1441–1449
Meek, M.D. (1998): Ah Receptor and Estrogen Receptor-Dependent Modulation of Gene Expression by Extracts of Diesel Exhaust Particles. Environ. Res. 79, 114–121
Jones, P.D.; Giesy, J.P.; Newsted, J.L.; Verbrugge, D.A.; Ludwig, J.P.; Ludwig, M.E.; Auman, HJ.; Crawford, R.; Tillitt, D.E.; Kubiak, T.J.; Best, D.A. (1994): Accumulation of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Equivalents by Double-Crested Cormorant (Phalacrocorax auritus, Pelicaniformes) Chicks in the North American Great Lakes. Ecotoxicol. Environ. Safety 27, 192–209
Murk, A.J.; Leonard, B.E.G.; Van Hattum, B.; Luit, R.; Van der Weiden, M.E.J.; Smit, M. (1998): Application of Biomarkers for Exposure and Effect of Polyhalogenated Aromatic Hydrocarbons in Naturally Exposed European Otters (Lutra lutra). Environ. Toxicol. Pharmacol. 6, 91–102
Safe, S. (1995): Environmental and Dietary Estrogens and Human Health: Is There a Problem? Environ. Health Perspect. 103, 346–351
Villeneuve, D.; Richter, C.A.; Giesy, J.P. (1999): Rainbow Trout Cell Bioassay Derived TEFs for Halogenated Aromatic Hydrocarbons: A Comparison and Sensitivity Analysis. Environ. Toxicol. Chem. 18, 879–888
Additional Literature
Hofmaier, A.; Markmann, A.; Lehnardt, R.; Schramm, K.-W.; Kaune, A.; Kettrup, A. (1998): Measuring TCDD Equivalents (TEQ) in Emission Samples from a Plant, Utilising Secondary Aluminium and Environmental Samples with a Bioassay. In: Dioxin ’98 — 18th Symposium on Halogenated Environmental Organic Pollutants/Formation and Sources, Transport and Fate (Eds.: N. Johansson et al.). Stockholm: Swedish Environmental Protection Agency, Organohalogen Compounds 36, 187–191
Hofmaier, A.M.; Schwirzer, S.M.G.; Wiebel, F.J.; Schramm, K.-W.; Wegenke, M.; Kettrup, A. (1998): Bioassay zur Bestimmung von TCDD-Toxizitätsäquivalenten (TEQ) von Umweltproben und Reststoffen. UWSF — Z. Umweltchem. Ökotox. 11, 2–8 (1998)
Klimm, C.; Hofmaier, A.M.; Schramm, K.-W.; Kettrup, A. (1999): Using TEF Concept for Assessing Toxic Potency of Polycyclic Aromatic Hydrocarbons in Industrial Samples. Organohalogen Compounds 40, 39–42
Li, W.; Wu, W.Z.; Beck, B.; Schramm, K.-W.; Kettrup, A. (1999): A New Enzyme Immunoassay for PCDD/F TEQ Screening In Environmental Samples: Comparison to Micro-Erod Assay and to Chemical Analysis. Chemosphere 38, 3313–3318
Li, W.; Wu, W.Z.; Schramm, K.-W.; Kettrup, A. (1999): Toxicity of Mixtures of Polychlorinated Dibenzo-p-dioxins, Dibenzofurans, and Biphenyls Determined by Dose-Response Curve Analysis. Bull. Environ. Toxicol. 62, 539–546
Rehmann, K.; Rudzki, M.; Schramm, K.-W.; Kettrup, A. (1999): Erfahrungen mit einem Hefe-Zest zum Nachweis von Östrogenrezeptor-aktivierenden Substanzen in Umweltproben. Ökotoxikologie (Ed. Oehlmann, Markert), ISBN 3-609-68370-8, ecomed, 538–545
Rehmann, K.; Schramm, K.-W; Kettrup, A. (1999): Applicability of a Yeast Oestrogen Screen for the Detection of Oestrogen-Like Activities in Environmental Samples. Chemosphere 38, 3303–3312
Rehmann, K.; Schramm, K.-W.; Kettrup, A. (1999): Soot as a Source of Estrogen- and Androgen Receptor Activating Compounds. Organohalogen Compounds 42, 105–108
Rehmann, K.; Wu, W.Z.; Schramm, K.-W.; Kettrup, A. (1999): Xenoestrogens in Unexpected Places — First Results from the Application of a Yeast Oestrogen Assay on Non Aqueous Environmental Samples. Proceedings Industrial Toxicology, ISSN 1335-3160, 129–131
Schramm, K.-W.; Hofmaier, A.; Klobasa, O.; Kaune, A.; Kettrup, A. (1999): Biological In Vitro Emission Control. J. of Analytical and Applied Pyrolysis 49, 199–210
Schramm, K.-W.; Hofmaier, A.; Klobasa, O.; Rehmann, K.; Kaune, A.; Wu, W.Z.; Kettrup, A. (1999): Biological In Vitro Investigation of Industrial (and Environmental) Samples. Proceedings Industrial Toxicology, ISSN 1335-3160, 22–30
Schwirzer, S.M.G.; Hofmaier, A.M.; Kettrup, A.; Nerdinger, P.E.; Schramm, K.-W.; Thoma, H.; Wegenke, M.; Wiebel, F.J. (1998): Establishment of a Simple Cleanup Procedure and Bioassay for Determining 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicity Equivalents of Environmental Samples. Ecotoxicology and Environmental Safety 41, 77–82
Wu, W.Z.; Schwirzer, S.M.G.; Schramm, K.-W; Wiebel, F.J.; Xu, Y.; Zhang, Y.Y.; Yediler, A.; Kettrup, A. (1996): Rapid Bioassay as Indicator of Potentially Harmful Effects for Dioxin-like Compounds in Sample of Ya-Er Lake, China: Requirements for Clean-up and Comparison to Chemical Analysis. Fresenius Envir. Bull. 5, 374–379
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hilscherova, K., Machala, M., Kannan, K. et al. Cell bioassays for detection of aryl hydrocarbon (AhR) and estrogen receptor (ER) mediated activity in environmental samples. Environ. Sci. & Pollut. Res. 7, 159–171 (2000). https://doi.org/10.1065/espr2000.02.017
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1065/espr2000.02.017