Environmental Toxicology and Ecotoxicology
Anders Goksøyr
professor, dr. scient.
UoB
Science
Faculty
MBI
Research
- Fjose
- Fladmark
- Goksøyr
- Helland
- Jensen
- Lillehaug
- Male
- Raae
- Seo
- Ziegler
- Walther
- Aasland
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Phone: +47 555 84374 |
Biotransformation enzymes are involved in the metabolism of foreign compounds (xenobiotics) from lipophilic substrates to more polar and water-soluble products. The ability of an organism to biotransform and excrete such compounds is an important factor in determining the effects of pollutants in the environment. However, intermediate products of these processes may be highly reactive and toxic to the cell e.g. by covalent binding to DNA, RNA or proteins (adducts) or by the production of reactive oxygen species (ROS). Furthermore, enzymes involved in this metabolism also have important roles in the metabolism of endogenous signal compounds such as steroids and fatty acids. Exposure to pollutants can thereby disturb delicate balances in hormone production and signal transduction.
Enzyme families under study in this context are the cytochrome P450 system (CYP), heme oxygenase (HO) and nitric oxide synthase (NOS), mainly in fish but also in marine mammals (seals, whales, polar bears), and invertebrates (crabs, mussels). We study how these enzymes are regulated by endogenous factors such as development, sexual reproduction and genetic (species) differences, and by exogenous factors, such as temperature, diet, and pollutant exposure.
Endocrine disruptors and reproductive toxicology
An important aspect of environmental toxicology is the study of how environmental pollutants can disturb hormonal balances and thereby influence reproductive processes in an organism. It has lately been shown that many compounds can mimick the natural hormone estradiol, and these xenoestrogens are able to induce estrogenic processes such as the synthesis of eggshell (zona radiata) protein and vitellogenin in fish liver in vivo. It is important to be able to relate these molecular processes to consequences at the level of population recruitment.
The mechanisms behind these effects are also being studied in collaboration with other groups at MBI.
Development of biomarkers
Many biotransformation enzymes and other proteins are inducible by exposure to different types of pollutants. This feature forms the basis of using such systems as biomarkers, i.e. biological responses that can indicate pollutant exposure. Such systems have a wide application both in ecotoxicological research and in monitoring programmes of the aquatic environment. The research on development of biomarkers includes studies of natural variability, dose-response experiments, time-course studies, and structure-activity relationships in experimental setups ranging from in vitro cell cultures to large-scale field studies. For biomarker development we also work with blue mussels Mytilus edulis.
Development of antibodies to biomarker proteins is another part of this research that has lead to the establishment of the company Biosense Laboratories AS at HIB. This company is devoted to the development, characterization and marketing of biomarker antibodies and antibody-kits, using hybridoma technology for monoclonal antibody production.
Methodology
The research in this group spans experiments in test tubes and cell cultures to aquaria and field studies for in vivo research. We use enzyme assays, immunoassays, and mRNA analyses and proteomic based methods to study different parameters in tissue fractions and in cell cultures. Protein purification work often includes chromatography, gel electrophoresis, enzymology and immunoassays. Immunoassays include ELISA, Western blotting and immunohistochemistry. Proteomic based methods (toxicoproteomics) includes studies of changes in protein patterns in by 2-dimensional gel-electrophoresis (2-DE). Protein spots with changed expression pattern are isolated and identity is sought by using different mass spectrometry methods to obtain fragment weights after trypsin digestion (MALDI) and de novo sequencing (ESI Q-ToF MS), combined with database searches (bioinformatics)
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2-D gel electrophoresis image library for toxicoproteomics 
Here we will post images of 2-D gels of tissues of target species and cell systems for our toxicoproteomics work, e.g. Atlantic cod (Gadus morhua), Atlantic salmon (Salmo salar), common carp (Cyrpinus carpio), African clawed frog (Xenopus laevis), blue mussel (Mytilus edulis), MVLN cells etc. Over time we will present images from different exposure situations and make links from identified protein spots to genomic databases.
Selected references:
Hasselberg L., Goksøyr A., Grøsvik B.E. Celander M Interactions between xenoestrogens and ketoconazole on CYP1A and CYP3A in juvenile Atlantic cod (Gadus morhua). Comparative Hepatology, 4:2 (2005).
Al-Arabi S.A.M., Adolfsson-Erici M., Waagbø R., Ali M.S., and Goksøyr A. Contaminant accumulation and biomarker responses in caged fish exposed to effluents from anthropogenic sources in the Karnaphuly River, Bangladesh. Environ. Toxicol. Chem., 24:1968-1978 (2005).
Goksøyr A. Endocrine disruptors in the marine environment: mechanisms of toxicity and their influence on reproductive processes in fish. J. Toxicol. Environ. Health part A, in press (2005).
Nilsen BM, Berg K, Eidem JK, Kristiansen SI, Brion F, Porcher JM, Goksøyr A. Development of quantitative vitellogenin-ELISAs for fish test species used in endocrine disruptor screening. Anal Bioanal Chem. 378:621-33 (2004).
Bemanian, V; Male, R. & Goksøyr, A. The Aryl hydrocarbon receptor-mediated disruption of vitellogenin synthesis in the fish liver: Cross-talk between AHR- and ERa-signaling pathways. Comparative Hepatology 3:2 (2004), http://www.comparative-hepatology.com.
Jonsson H, Sandnes KV, Schiedek D, Schneider R, Grøsvik BE, Goksøyr A. Development of two novel CYP-antibodies and their use in a PCB exposure experiment with Mytilus edulis. Mar Environ Res. 58(2-5):655-8 (2004).
Mandich A, E. Benfenati, MT Cronin, A Goksøyr, BE Grøsvik, W Kloas, A Van Cauwenberge, L Vigano. 2005. Environmental agent susceptibility assessment using existing and novel biomarkers as rapid noninvasive testing methods. Ann N Y Acad Sci. 1040:381-6.
Rodriguez-Ortega MJ, Grøsvik BE, Rodriguez-Ariza A, Goksøyr A & Lopez-Barea J. changes in protein expression profiles in bivalve molluscs (Chamaelea gallina) exposed to four model environmental pollutants. Proteomics 3, 1535-1543 (2003).
Arukwe A. , Goksøyr A. (2003). "Eggshell and egg yolk proteins in fish: hepatic proteins for the next generation. Oogenetic, population, and evolutionary implications of endocrine disruption." Comparative Hepatology 2: 4.
Al-Arabi S.A.M. , Goksøyr A. (2002). "Cytochrome P4501A responses in two tropical fish species, riverine catfish (Rita rita) and marine mudfish (Apocryptes bato)." Comp. Biochem. Physiol. 131c: 61-71.
Arukwe A., K. S. W., Berg K., Goksøyr A. & Hinton D.E. B (2002). "Molecular cloning of rainbow trout (Onco-rhynchus mykiss) eggshell zona radiata protein complementary DNA: mRNA expression in 17beta-estradiol- and nonylphenol-treated fish." Comp. Biochem. Physiol. 132: 315-326.
Boon JP, v. Z. J., Lewis WE, Zegers BN, Goksoyr A, Arukwe A. (2002). "The expression of CYP1A, vitellogenin and zona radiata proteins in Atlantic salmon (Salmo salar) after oral dosing with two commercial PBDE flame retardant mixtures: absence of short-term responses." Mar Environ Res. 54: 719-724.
Brion F., N. B. M., Eidem J.K., Goksøyr A. & Porcher J. M. (2002). "Development and validation of an enzyme- linked immunsorbent assay to measure vitellogenin in the zebrafish (Danio rerio)." Environ. Toxicol. Chem. 28: 1699-1708.
Arukwe A., Y., F., Male. R. and A. Goksøyr. (2001). "Modulation of xenoestrogen-induced zonagenesis and vitel-logenesis by the antiestrogen, 3,3´4,4´-tetrachlorobiphenyl (PCB-77) in juvenile fish." Environ. Toxicol. Phar-macol. 10: 5-15.
Boon J.P., L. W. E. G. A. (2001). "Immunochemical and catalytic characterization of hepatic microsomal cytochrome P450 in the sperm whale (Physeter macrocephalus)." Aquat. Toxicol. 52: 297-309.
Jørgensen E.H., C. M., Goksøyr A. & Iwata M. (2001). "The effect of stress on toxicant-dependent cytochrome P450 enzyme responses in the Arctic charr (Salvelinus alpinus)." Environ. Toxicol. Chem. 20: 2523-2529.
Lundebye A.-K., A. G. A. M. (2001). Kontaminanter. Kap. i Fiskeernæring (R. Waagbø, M. Espe, K. Hamre & Ø. Lie, eds.), Kystnæringen Forlag & Bokklubb.
Holmqvist, B., Ellingsen B., Alm P., Forsell J., Øyan A.M., Goksøyr A., Fjose A. & H. Seo. (2000). "Identification and distribution of nitric oxide synthase in the brain of adult zebrafish." Neurosci Lett 292: 119-122.
Arukwe A., T. R., Ingebrigtsen K., Celius T., Goksøyr A. & Cravedi J.-P. I (2000). "In vivo and in vitro metabolism and organ distribution of nonylphenol in Atlantic salmon (Salmo salar)." Aquat. Toxicol. 49: 289-304.
Utne Skaare J., B. A., Derocher A., Gabrielsen G.W., Goksøyr A., Henriksen E., Larsen H.J., Lie E. & Wiig Ø. (2000). "Organochlorines in top predators at Svalbard - occurence, levels and effects." Toxicol. Lett. 112-113(103-109).
Øyan A. M., N. F., Goksøyr A. & Holmqvist B. (2000). "Partial cloning of constitutive and inducible nitric oxide synthases and detailed neuronal expression of NOS mRNA in the cerebellum and optic tectum of adult Atlan-tic salmon (Salmo salar)." Mol. Brain Research 78: 38-49.
Arukwe, A., B.M. Nilsen, K. Berg and A. Goksøyr. Immunohistochemical analysis of the vitellogenin response in the liver of Atlantic salmon exposed to environmental estrogens. Biomarkers, 4: 373-380 (1999).
Goksøyr A. and A.-M. Husøy (1998) Immunochemical approaches to studies of CYP1A localization and induction by xenobiotics in fish. In: “Fish Ecotoxicology”) (Braunbeck T., D.E. Hinton & B. Streit, eds.) Birkhäuser Verlag, Basel, p 165-202
Grøsvik B.E., H.E. Larsen & A. Goksøyr 1997. Effect of piperonyl butoxide and ß-naphthoflavone on cytochrome P450 1A expression and activity in Atlantic salmon (Salmo salar). A temperature and time study. Environmental Toxicology and Chemistry. 16; 415-423.
Arukwe A., Knudsen F.R. & Goksøyr A. Fish zona radiata (eggshell) protein: A sensitive biomarker for environmental estrogens. Environ. Health Persp. 104, 418-422 (1997).
Celander M., Buhler D.R., Förlin L., Goksøyr A., Miranda C.L., Woodin B.R. & Stegeman J.J. Immunochemical relationships of cytochrome P450 3A-like proteins in teleost fish. Fish Physiol. Biochem., 15, 323-332 (1996).
Gadagbui B. & Goksøyr A. CYP1A and other biomarker responses to effluents from a textile mill in the Volta River (Ghana) using caged tilapia (Oreochromis niloticus) and sediment-exposed mudfish (Clarias anguillaris). Biomarkers, 1, 252-261 (1996).
Grøsvik B.E. & Goksøyr A. Biomarker protein expression in primary cultures of salmon (Salmo salar) hepatocytes exposed to environmental pollutants. Biomarkers, 1, 45-53 (1996).
Goksøyr A. Cytochrome P450 in marine mammals: isozyme forms, catalytic functions, and physiological regulations. Dev. Mar. Biol. 4, pp. 629-639 (1995).
Books in popular science:
A. Goksøyr. Genenes tidsalder. Om DNA, mennesket og genteknologien. Alma Mater forlag, 160 s., 1994.
A. Goksøyr. DNA. Det mystiske arvestoffet. Gyldendal Tiden forlag, 48 s., 2000, (2. utgave 2004) svensk utgave: DNA – den mystiska arvsmassan. Alfabeta Bokforlag, 2001 tysk utgave, under utgivelse
