Induction of cytochrome P450 as a biomarker for environmental contamination in aquatic ecosystems

Abstract Representing toxicant‐induced changes in biological systems, biomarkers can serve as linkers between contamination (cause) and biological effects, and therefore provide unique information on ecosystem health. Hence, they are increasingly used for assessing the exposure of organisms to environmental contamination. Here, application of the induction of cytochrome P4501A (CYP1A), certainly the best studied biomarker, in field trials with freshwater and marine fish is reviewed. Moreover, the use of a number of other biomarkers, alone or in concert with CYP1A, is evaluated. Determination of CYP1A in field studies with fish has to consider several influencing factors, such as species, age, reproductive stage, temperature, and possible inhibitors. The overview shows that CYP1A induction is significantly related to contaminant levels in the environment in 93% of the investigated field studies. It is apparent that only certain classes of xenobiotica act as inducers of CYP1A (e.g., PAHs, coplanar PCBs, pol...

[1]  R. Peterson,et al.  2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Toxicity during Early Life Stage Development of Lake Trout (Salvelinus namaycush) , 1991 .

[2]  Michael N Moore.  Pollutant-induced cell injury in fish liver: Use of fluorescent molecular probes in live hepatocytes , 1992 .

[3]  G. Pickwell,et al.  Induction of HSP70 proteins in mussels by ingestion of tributyltin , 1993 .

[4]  D. Muir,et al.  Indications of P450 monooxygenase activities in beluga (Delphinapterus leucas) and narwhal (Monodon monoceros) from patterns of PCB, PCDD and PCDF accumulation , 1992 .

[5]  C. Houghton,et al.  A comparison of the levels of hepatic aryl hydrocarbon hydroxylase in fish caught close to and distant from north sea oil fields , 1984 .

[6]  A. Goksøyr,et al.  Effects of 2,3,7,8-TCDD and contaminated sediment on the cytochrome P4501A orthologue in rainbow trout (Oncorhynchus mykiss) and carp (Cyprinus carpio), using catalytic and immunochemical techniques , 1992 .

[7]  A. Goksøyr,et al.  Changes in levels of hepatic biotransformation enzymes and haemoglobin levels in female plaice (Pleuronectes platessa) after oral administration of a technical polychlorinated biphenyl mixture (Clophen A40). , 1992, The Science of the total environment.

[8]  B. Ames,et al.  Carcinogenesis mechanisms: the debate continues. , 1991, Science.

[9]  J. Stegeman,et al.  Effects of temperature acclimation on the expression of hepatic cytochrome P4501A mRNA and protein in the fish Fundulus heteroclitus. , 1992, Archives of biochemistry and biophysics.

[10]  W. Welch,et al.  Relationships between accumulation of a 60 kDa stress protein and scope-for-growth in Mytilus edulis exposed to a range of copper concentrations , 1991 .

[11]  S. Brown,et al.  STUDIES OF A FATAL POLLUTANT-INDUCED HYPERBILIRUBINAEMIA IN SPAWNING ATLANTIC SALMON , 1992 .

[12]  D. Nebert,et al.  Trout P450IA1: cDNA and deduced protein sequence, expression in liver, and evolutionary significance. , 1988, DNA.

[13]  J. Albaigés,et al.  7-ethoxyresorufin O-deethylase (EROD) and antioxidant enzyme activities in larvae of sardine (Sardina pilchardus) from the north coast of Spain , 1994 .

[14]  G. Monod,et al.  Glucocorticoid-mediated potentiation of P450 induction in primary culture of rainbow trout hepatocytes. , 1992, Biochemical pharmacology.

[15]  R. Voss,et al.  A survey of pulp and paper mill effluents for their potential to induce mixed function oxidase enzyme activity in fish , 1994 .

[16]  W. Penrose,et al.  Induction of aryl hydrocarbon (benzo[a]pyrene) hydroxylase in fish by petroleum , 1975, Bulletin of environmental contamination and toxicology.

[17]  P. Kloepper-Sams,et al.  BIOINDICATOR FIELD MONITORING : USE OF FISH BIOCHEMICAL PARAMETERS AT A MODERN BLEACHED KRAFT PULP MILL SITE , 1992 .

[18]  W. Seinen,et al.  Concurrence of P450 lAl induction and toxic effects after administration of a low dose of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) in the rainbow trout (Oncorhynchus mykiss) , 1992 .

[19]  F. Galgani,et al.  Ethoxyresorufin-O-deethylase (EROD) activity in flatfish: Fast determination with a fluorescence plate-reader , 1992 .

[20]  M. M. Krahn,et al.  Toxic chemicals, including aromatic and chlorinated hydrocarbons and their derivatives, and liver lesions in white croaker (Genyonemus lineatus) from the vicinity of Los Angeles. , 1987, Environmental science & technology.

[21]  W. Seinen,et al.  Induction of cytochrome P450 1A in fish treated with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin or chemically contaminated sediment , 1993 .

[22]  S. Dyer,et al.  A Laboratory Evaluation of the Use of Stress Proteins in Fish to Detect Changes in Water Quality , 1993 .

[23]  D. Holdway,et al.  MFO activity in carp (Cyprinus carpio) exposed to treated pulp and paper mill effluent in Lake Coleman, Victoria, Australia, in relation to AOX, EOX, and muscle PCDD/PCDF , 1994 .

[24]  E. Quardokus,et al.  Hepatic CYP1A1 Induction in Rainbow Trout by Continuous Flowthrough Exposure to β-Naphthoflavone , 1993 .

[25]  L. Johnson,et al.  Chemical contaminants and hepatic lesions in winter flounder (Pleuronectes americanus) from the Northeast coast of the United States , 1993 .

[26]  P. Goering,et al.  Stress protein synthesis induced in rat liver by cadmium precedes hepatotoxicity. , 1993, Toxicology and applied pharmacology.

[27]  M. Ronis,et al.  The use of polyclonal antibodies raised against rat and trout cytochrome P450 CYP1A1 orthologues to monitor environmental induction in the channel catfish (Ictalurus punctatus) , 1992 .

[28]  G. Perdew,et al.  Detection of the Ah receptor in rainbow trout: use of 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin in cell culture. , 1991, Toxicology letters.

[29]  K. Shepard,et al.  The use of bioindicators for assessing the effects of pollutant stress on fish , 1989 .

[30]  R. Keller,et al.  Effect of exposure to atmospheric air on blood glucose and lactate concentrations in two crustacean species: A role of the Crustacean hyperglycemic hormone (CHH) , 1993 .

[31]  C. M. Marn,et al.  Use of mixed-function oxygenases to monitor contaminant exposure in wildlife , 1989 .

[32]  M. E. Hahn,et al.  Effects of ortho- and non-ortho-substituted polychlorinated biphenyl congeners on the hepatic monooxygenase system in scup (Stenotomus chrysops). , 1989, Toxicology and applied pharmacology.

[33]  L. Hightower.  A brief perspective on the heat-shock response and stress proteins , 1993 .

[34]  W. Welch,et al.  How cells respond to stress. , 1993, Scientific American.

[35]  J. Lech,et al.  Biotransformation and induction: implications for toxicity, bioaccumulation and monitoring of environmental xenobiotics in fish. , 1987, Environmental health perspectives.

[36]  L. Fishelson,et al.  The effects of aroclor 1254 and petrochemical pollutants on cytochrome P450 from the digestive gland microsomes of four species of mediterranean molluscs , 1992 .

[37]  J. Giesy,et al.  H4IIE rat hepatoma cell bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in colonial fish-eating waterbird eggs from the Great Lakes , 1991, Archives of environmental contamination and toxicology.

[38]  R. Cousins.  Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. , 1985, Physiological reviews.

[39]  A. Oikari,et al.  Changes of the liver UDP-glucuronosyltransferase activity in trout (Salmo gairdneri Rich.) acutely exposed to selected aquatic toxicants. , 1987, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[40]  E. Nikunen.  Toxic impact of effluents from petrochemical industry. , 1985, Ecotoxicology and environmental safety.

[41]  J. Stegeman,et al.  Detoxication enzymes as indicators of environmental stress on fish , 1990 .

[42]  L. Förlin,et al.  Induction of cytochrome P450 1A in teleosts: environmental monitoring in Swedish fresh, brackish and marine waters , 1993 .

[43]  C. Beltrame,et al.  The micronucleus test: examples of application to marine ecology , 1988 .

[44]  J. Narbonne,et al.  Effects of benzo(a)pyrene, 3,3′,4,4′-tetrachlorobiphenyl and 2,2′,4,4′,5,5′-hexachlorobiphenyl on the xenobiotic-metabolizing enzymes in the mussel (Mytilus galloprovincialis) , 1993 .

[45]  É. Vindimian,et al.  Effect of storage conditions and subcellular fractionation of fish liver on cytochrome p-450-dependent enzymatic activities used for the monitoring of water pollution , 1991 .

[46]  C. Miranda,et al.  Multiple effects of 3,4,5,3',4',5'-hexachlorobiphenyl administration on hepatic cytochrome P450 isozymes and associated mixed-function oxidase activities in rainbow trout. , 1990, Biochemical pharmacology.

[47]  J. Lech,et al.  Induction of hepatic microsomal monooxygenase activity in fish by exposure to river water , 1987 .

[48]  J. Stegeman,et al.  Hepatic and extrahepatic microsomal electron transport components and mixed-function oxygenases in the marine fish Stenotomus versicolor. , 1979, Biochemical pharmacology.

[49]  J. Stegeman,et al.  Specificity and cross-reactivity of monoclonal and polyclonal antibodies against cytochrome P-450E of the marine fish scup. , 1987, Archives of biochemistry and biophysics.

[50]  D. Livingstone,et al.  Cytochrome P-450 monooxygenase system and benzo(a)pyrene metabolism in echinoderms , 1990 .

[51]  David E. Williams,et al.  Sensitivity of cytochrome P450-1A1 induction in fish as a biomarker for distribution of TCDD and TCDF in the Willamette River, Oregon , 1993 .

[52]  D. Zandee,et al.  A field study on stress indices in the sea mussel,Mytilus edulis: Application of the “stress approach” in biomonitoring , 1991, Archives of environmental contamination and toxicology.

[53]  G. Mcmahon,et al.  Mutations in c-Ki-ras oncogenes in diseased livers of winter flounder from Boston Harbor. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[54]  R. Larossa,et al.  The Cellular Functions of Chaperonins , 1990 .

[55]  J. Lech,et al.  Dose-effect relationship for induction of hepatic monooxygenase activity in rainbow trout and carp by Aroclor 1254 , 1983 .

[56]  J. Stegeman.  Benzo[a]pyrene oxidation and microsomal enzyme activity in the mussel (Mytilus edulis) and other bivalve mollusc species from the Western North Atlantic , 1985 .

[57]  J. Stegeman,et al.  Effects of tributyltin chloride in vitro on the hepatic microsomal monooxygenase system in the fish Stenotomus chrysops , 1991 .

[58]  J. Garric,et al.  Freshwater fish cytochrome P450-dependent enzymatic activities: a chemical pollution indicator. , 1989, Ecotoxicology and Environmental Safety.

[59]  A. Oikari,et al.  Biotransformation and other physiological responses in whitefish caged in a lake receiving pulp and paper mill effluents. , 1989, Ecotoxicology and environmental safety.

[60]  Ȧ. Larsson,et al.  Long-term effects of bleached kraft mill effluents on carbohydrate metabolism and hepatic xenobiotic biotransformation enzymes in fish. , 1987, Ecotoxicology and environmental safety.

[61]  T. Collier,et al.  Bioindicators of contaminant exposure and sublethal effects: Studies with benthic fish in puget sound, Washington , 1992 .

[62]  S. Courtenay,et al.  Induction and clearance of cytochrome P4501A mRNA in Atlantic tomcod caged in bleached kraft mill effluent in the Miramichi River , 1993 .

[63]  Seasonal Effects of Bleached Kraft Mill Effluent on Reproductive Parameters of White Sucker (Catostomus commersoni) Populations of the St. Maurice River, Quebec, Canada , 1994 .

[64]  R. Addison,et al.  THE UTILIZATION OF CYTOCHROME P4501A MRNA IN LIMANDA LIMANDA (DAB) AS A MONITOR OF CHEMICAL EXPOSURE IN THE NORTH SEA , 1992 .

[65]  J. Bertrand,et al.  Effects of petroleum hydrocarbons on the cytochrome P450 content of the mollusc bivalveMytilus galloprovincialis , 1984 .

[66]  S. Hamilton,et al.  Metallothionein in Fish: Review of Its Importance in Assessing Stress from Metal Contaminants , 1986 .

[67]  O. Hänninen,et al.  Temperature compensation of hepatic microsomal cytochrome P-450 activity in rainbow trout. I: Thermodynamic regulation during water cooling in autumn , 1989 .

[68]  E. Gallagher,et al.  Effects of Black Rock Harbor sediments on indices of biotransformation, oxidative stress, and DNA integrity in channel catfish , 1993 .

[69]  H. Sikka,et al.  Xenobiotic metabolizing enzyme activity in the liver and kidney of the brown bullhead (Ictalurus nebulosus) , 1992 .

[70]  E. Craig,et al.  Heat shock proteins: molecular chaperones of protein biogenesis , 1993, Microbiological reviews.

[71]  N. Vermeulen,et al.  Interrelationships between bioaccumulation of organic trace pollutants (PCBs, organochlorine pesticides and PAHs), and MFO-induction in fish. , 1991, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[72]  A. Oikari,et al.  Bleached kraft pulpmill effluents and TCDD: Effects on biotransformation and testosterone status of mature male rainbow trout (Salmo gairdneri) , 1989 .

[73]  J. Stegeman,et al.  Cytochrome P450E (P450IA) induction and inhibition in winter flounder by 3,3′,4,4′‐tetrachlorobiphenyl: Comparison of response in fish from georges bank and narragansett bay , 1991 .

[74]  W. Salvenmoser,et al.  Effects of treated paper mill effluents on hepatic morphology in male bullhead (Cottus gobio L.) , 1992 .

[75]  L. Förlin,et al.  Influence of biological and environmental factors on hepatic steroid and xenobiotic metabolism in fish: interaction with PCB and β-naphthoflavone , 1984 .

[76]  N. B. White,et al.  Biochemical Evidence that Winter Flounder (Pseudopleuronectes americanus) have Induced Hepatic Cytochrome P-450-Dependent Monooxygenase Activities , 1983 .

[77]  J. Stegeman,et al.  Induction of hepatic cytochrome p-450 in fish and the indication of environmental induction in scup (Stenotomus chrysops) , 1981 .

[78]  M. E. Hahn,et al.  Cytochrome P4501A induction and inhibition by 3,3',4,4'-tetrachlorobiphenyl in an Ah receptor-containing fish hepatoma cell line (PLHC-1) , 1993 .

[79]  A. Şen,et al.  Effects of in vivo benzene treatment on cytochrome P450 and mixed-function oxidase activities of gilthead seabream (sparus aurata) liver microsomes , 1993 .

[80]  W. Williams,et al.  The effects of polychlorinated biphenyls on plasma steroid levels and hepatic microsomal enzymes in fish , 1978 .

[81]  J. Stegeman,et al.  Uptake, toxicity, and distribution of benzo[a]pyrene and monooxygenase induction in the topminnows Poeciliopsis monacha and Poeciliopsis lucida. , 1987, Drug metabolism and disposition: the biological fate of chemicals.

[82]  J. Payne.  Field evaluation of benzopyrene hydroxylase induction as a monitor for marine petroleum pollution. , 1976, Science.

[83]  Ȧ. Larsson,et al.  Physiological Disturbances in Fish Living in Coastal Water Polluted with Bleached Kraft Pulp Mill Effluents , 1988 .

[84]  D. Hinton,et al.  Liver structural alterations accompanying chronic toxicity in fishes: Potential biomarkers of exposure , 1988 .

[85]  J. Stegeman,et al.  Monooxygenase Induction and Chlorobiphenyls in the Deep-Sea Fish Coryphaenoides armatus , 1986, Science.

[86]  J. Bach,et al.  The effects of temperature on the basal activity of cytochrome P-450 in rainbow trout (Salmo gairdneri) , 1990 .

[87]  M. E. Hahn,et al.  Immunohistochemical localization of cytochrome P-450IA1 induced by 3,3',4,4'-tetrachlorobiphenyl and by 2,3,7,8-tetrachlorodibenzoafuran in liver and extrahepatic tissues of the teleost Stenotomus chrysops (scup). , 1991, Drug metabolism and disposition: the biological fate of chemicals.

[88]  L. Hightower,et al.  Evaluation of heavy‐metal ion toxicity in fish cells using a combined stress protein and cytotoxicity assay , 1994 .

[89]  M. Zafarullah,et al.  Endogenous and heavy-metal-ion-induced metallothionein gene expression in salmonid tissues and cell lines. , 1989, Gene.

[90]  J. Stegeman,et al.  Time-course and dose-response of the apparent induction of the cytochrome P450 monooxygenase system of pyloric caeca musomes of the female sea star Asterias rubens L. by benzo[a]pyrene and polychlorinated biphenyls , 1993 .

[91]  D. Bevan,et al.  DNA adducts detected in muskrats by 32P‐postlabeling analysis , 1992 .

[92]  S. Adams,et al.  Responses of fish populations and communities to pulp mill effluents: a holistic assessment. , 1992, Ecotoxicology and environmental safety.

[93]  A. Goksøyr,et al.  Effects of Dietary Iron Concentrations on the Cytochrome P450 System of Atlantic Salmon (Salmo salar) , 1994 .

[94]  M. Kietzmann.  Biological markers in reproductive toxicology: National Research Council (U.S.), Subcommittee on Reproductive Toxicology. XXI + 395 pp. Washington: National Academy Press (1989) , 1992 .

[95]  Chemical contamination and associated fish diseases in San Diego Bay , 1992 .

[96]  H. Issaq,et al.  Induction of hepatic CYP1A activity as a biomarker for environmental exposure to Aroclor® 1254 in feral rodents , 1992, Archives of environmental contamination and toxicology.

[97]  W. Slooff,et al.  Relative liver weights and xenobiotic-metabolizing enzymes of fish from polluted surface waters in the Netherlands , 1983 .

[98]  D. Hoffman,et al.  Biomarkers of contaminant exposure in common terns and black‐crowned night herons in the Great Lakes , 1993 .

[99]  U. Varanasi,et al.  32P-postlabeling analysis of DNA adducts in liver of wild English sole (Parophrys vetulus) and winter flounder (Pseudopleuronectes americanus). , 1989, Cancer research.

[100]  J. Lech,et al.  Negative control of cytochrome P450 1A1 (CYP1A1) by glucocorticoids in rainbow trout liver. , 1993, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[101]  J. Stegeman,et al.  Biomonitoring environmental contamination with pipping black-crowned night heron embryos: Induction of cytochrome P450 , 1993 .

[102]  A. Goksøyr,et al.  The cytochrome P450 1A1 response in fish: application of immunodetection in environmental monitoring and toxicological testing , 1992 .

[103]  P. E. Gibbs,et al.  The effect of tributyltin upon steroid titres in the female dogwhelk, Nucella lapillus, and the development of imposex , 1991 .

[104]  S. Lindquist.  The heat-shock response. , 1986, Annual review of biochemistry.

[105]  P. Béland,et al.  Aromatic DNA-carcinogen adducts in beluga whales from the Canadian Arctic and Gulf of St Lawrence , 1991 .

[106]  A. C. Dey,et al.  Selectivity of mixed-function oxygenase enzyme induction in flounder (Pseudopleuronectes americanus) collected at the site of the Baie Verte, Newfoundland oil spill. , 1984, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[107]  R. Kothary,et al.  Induction of a novel set of polypeptides by heat shock or sodium arsenite in cultured cells of rainbow trout, Salmo gairdnerii. , 1982, Canadian journal of biochemistry.

[108]  S. George,et al.  Cadmium effects on plaice liver xenobiotic and metal detoxication systems: dose-response , 1989 .

[109]  O. Hänninen,et al.  Unbleached pulp mill effluents affect cytochrome P450 monooxygenase enzyme activities , 1992 .

[110]  M. E. Hahn,et al.  Induction of cytochrome P-450E (P-450IA1) by 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF) in the marine fish scup (Stenotomus chrysops) , 1989 .

[111]  L. Migliore,et al.  Induction of micronuclei in gill tissue of Mytilus galloprovincialis exposed to polluted marine waters , 1990 .

[112]  B. Kurelec,et al.  Activity of benzo[a]pyrene monooxygenase in fish from the Sava River, Yugoslavia: correlation with pollution. , 1983, The Science of the total environment.

[113]  E. Gallagher,et al.  Effects of complex waste mixtures on hepatic monooxygenase activities in brown bullheads (Ictalurus nebulosus). , 1989, Environmental pollution.

[114]  J. Stegeman,et al.  Experimental and environmental induction of cytochrome P450E in fish from Bermuda waters , 1990 .

[115]  P. Baumann,et al.  Enlarged livers and hepatic microsomal mixed‐function oxidase components in tumor‐bearing brown bullheads from a chemically contaminated river , 1985 .

[116]  A. Oikari,et al.  Biotransformation and other toxicological and physiological responses in rainbow trout (Salmo gairdneri Richardson) caged in a lake receiving effluents of pulp and paper industry , 1990 .

[117]  F. Galgani,et al.  EROD measurements in fish from the northwest part of France , 1991 .

[118]  B. Sanders,et al.  Stress proteins in aquatic organisms: an environmental perspective. , 1993, Critical reviews in toxicology.

[119]  R. Irby,et al.  Effects of copper and tributyltin on stress protein abundance in the rotifer Brachionus plicatilis. , 1991, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[120]  P. Namour,et al.  In situ pollution induced cytochrome P450 activity of freshwater fish: barbel (Barbus barbus), chub (Leuciscus cephalus) and nase (Chondrostoma nasus) , 1991 .

[121]  Robert J. Huggett,et al.  Induced cytochrome P-450 in intestine and liver of spot (Leiostomus xanthurus) from a polycyclic aromatic hydrocarbon contaminated environment , 1990 .

[122]  T. Collier,et al.  Hepatic cytochrome P-450 isozymes and aryl hydrocarbon hydroxylase in English sole (Parophrys vetulus). , 1986, Biochemical pharmacology.

[123]  J. Stegeman,et al.  Effects of tributyltin in vivo on hepatic cytochrome P450 forms in marine fish , 1993 .

[124]  J. Henderson,et al.  Influence of dietary PUFA content on cytochrome P450 and transferase activities in atlantic salmon (salmo salar) , 1992 .

[125]  J. Stegeman,et al.  Cytochrome P-450 isozymes and monooxygenase activity in aquatic animals. , 1987, Environmental health perspectives.

[126]  M. E. Hahn,et al.  Photoaffinity labeling of the Ah receptor: phylogenetic survey of diverse vertebrate and invertebrate species. , 1994, Archives of biochemistry and biophysics.

[127]  J. H. Dewaide,et al.  Seasonal variation of hepatic drug metabolism in the roach, Leuciscus rutilus L. , 1970, Comparative biochemistry and physiology.

[128]  J. Albaigés,et al.  Responses of mixed-function oxygenase and antioxidase enzyme system of Mytilus sp. to organic pollution. , 1991, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[129]  C. Elcombe,et al.  Induction and characterization of hemoprotein(s) P-450 and monooxygenation in rainbow trout (Salmo gairdneri). , 1979, Toxicology and applied pharmacology.

[130]  S. Dyer,et al.  Synthesis and accumulation of stress proteins in tissues of arsenite‐exposed fathead minnows (Pimephales promelas) , 1993 .

[131]  P. H. Bach,et al.  Effects of arsenite on hepatic mixed-function oxidase activity in rats. , 1992, Xenobiotica; the fate of foreign compounds in biological systems.

[132]  I. M. Jones,et al.  Variability in the frequency of sister-chromatid exchange in larvae of Mytilus edulis: implications for field monitoring , 1987 .

[133]  T. Collier,et al.  Using cytochrome P450 to monitor the aquatic environment: Initial results from regional and national surveys , 1992 .

[134]  P. Lemaire,et al.  Interactive effects of cadmium and benzo(a)pyrene on cellular structure and biotransformation enzymes of the liver of the European eel Anguilla anguilla , 1992 .

[135]  M. E. Hahn,et al.  The Ah receptor in marine animals: phylogenetic distribution and relationship to cytochrome P4501A inducibility , 1992 .

[136]  K. Mazzucco,et al.  Biomonitoring of pollution: the hepatic cytochrome P-450 enzyme system in the feral mouse Apodemus flavicollis as indicator , 1994 .

[137]  D. Winge,et al.  Distinct metal-binding configurations in metallothionein. , 1985, The Journal of biological chemistry.

[138]  Richard F. Lee,et al.  Pollutant effects on the mixed function oxygenase (MFO) and reproductive systems of the marine polychaeteNereis virens , 1984 .

[139]  R. Ebel,et al.  Effects of naphthalene on benzo[a]pyrene hydroxylase and cytochrome P-450 in Fundulus heteroclitus , 1983 .

[140]  W. Müller,et al.  Benzo(a)pyrene monooxygenase induction in marine fish-molecular response to oil pollution , 1977 .

[141]  M. Pesonen,et al.  Expression of P4501A1 in a primary culture of rainbow trout hepatocytes exposed to beta-naphthoflavone or 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1992, Archives of biochemistry and biophysics.

[142]  L. Förlin,et al.  Induction of cytochrome P450 1A1 and conjugating enzymes in rainbow trout (Oncorhynchus mykiss) liver : a time course study , 1993 .

[143]  G. Monod,et al.  Effects of chemical pollution on the activities of hepatic xenobiotic metabolizing enzymes in fish from the River Rhône. , 1988, The Science of the total environment.

[144]  M. Leaver,et al.  Fish metallothioneins: Molecular cloning studies and induction in cultured cells , 1989 .

[145]  P. Zachariah,et al.  Hepatic Biotransformation of Environmental Xenobiotics in Six Strains of Rainbow Trout (Salmo gairdneri) , 1976 .

[146]  W. Seinen,et al.  Cytochrome P450 1A induction in the common carp (Cyprinus carpio) following exposure to contaminated sediments with halogenated polyaromatics , 1993 .

[147]  Hepatic EROD activity in spot, Leiostomus xanthurus, exposed to creosote-contaminated sediments , 1992 .

[148]  E. Glover,et al.  Variation in the molecular mass of the Ah receptor among vertebrate species and strains of rats. , 1987, Biochemical and biophysical research communications.

[149]  H. Tsuda,et al.  MOLECULAR FORMS OF GLUTATHIONE S‐TRANSFERASE AND UDP‐GLUCURONYLTRANSFERASE AS HEPATIC PRENEOPLASTIC MARKER ENZYMES a , 1983, Annals of the New York Academy of Sciences.

[150]  C. A. James,et al.  Ethoxyresorufin-O-deethylase and porphyrin analysis in chicken embryo hepatocyte cultures with a fluorescence multiwell plate reader. , 1993, Analytical biochemistry.

[151]  B. Sanders,et al.  Stress proteins as biomarkers of contaminant exposure in archived environmental samples. , 1993, The Science of the total environment.

[152]  P. Kloepper-Sams,et al.  Exposure of fish to biologically treated bleached-kraft effluent. 2. Induction of hepatic cytochrome P4501A in mountain whitefish (Prosopium williamsoni) and other species , 1994 .

[153]  M. Mckee,et al.  Alkoxyresorufin metabolism in white-footed mice at relevant environmental concentrations of Aroclor 1254. , 1992, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[154]  C. Portt,et al.  Response of hepatic MFO activity and plasma sex steroids to secondary treatment of bleached kraft pulp mill effluent and mill shutdown , 1992 .

[155]  M. James,et al.  Effect of 3-methylcholanthrene on monooxygenase, epoxide hydrolase, and glutathione S-transferase activities in small estuarine and freshwater fish , 1988 .

[156]  Livingstone.  Responses Of Microsomal Nadph-Cytochrome-C Reductase-Activity And Cytochrome-P-450 In Digestive Glands Of Mytilus-Edulis And Littorina-Littorea To Environmental And Experimental Exposure To Pollutants , 1988 .

[157]  W. Welch,et al.  Characterization of the thermotolerant cell. II. Effects on the intracellular distribution of heat-shock protein 70, intermediate filaments, and small nuclear ribonucleoprotein complexes , 1988, The Journal of cell biology.

[158]  S. De Flora,et al.  Genotoxic, carcinogenic, and teratogenic hazards in the marine environment, with special reference to the Mediterranean Sea. , 1991, Mutation research.

[159]  D. Livingstone.  Responses of the detoxication/toxication enzyme systems of molluscs to organic pollutants and xenobiotics , 1985 .

[160]  E. Candido,et al.  Transgenic hsp 16‐Lacz strains of the soil nematode caenorhabditis elegans as biological monitors of environmental stress , 1994 .

[161]  C. Walsh,et al.  An alternative 7-ethoxyresorufin O-deethylase activity assay: a continuous visible spectrophotometric method for measurement of cytochrome P-450 monooxygenase activity. , 1984, Analytical biochemistry.

[162]  M. Pesonen,et al.  Differential induction of cytochrome P-450-dependent monooxygenase, epoxide hydrolase, glutathione transferase and UDP glucuronosyl transferase activities in the liver of the rainbow trout by beta-naphthoflavone or Clophen A50. , 1985, Biochemical pharmacology.

[163]  T. Andersson,et al.  Differences in metallothionein gene expression in primary cultures of rainbow trout hepatocytes and the RTH-149 cell line. , 1990, Biochimica et biophysica acta.

[164]  P. Kremers,et al.  Induction and characterization of cytochromes P450IA and -IIB in the newt, Pleurodeles waltl. , 1992, Ecotoxicology and environmental safety.

[165]  P. Olsson,et al.  Increased hepatic metallothionein content correlates to cadmium accumulation in environmentally exposed perch (Perca fluviatilis) , 1986 .

[166]  K. Fent,et al.  Inhibition of hepatic microsomal monooxygenase system by organotins in vitro in freshwater fish , 1994 .

[167]  R. Huggett,et al.  Hepatic neoplasms in the mummichog Fundulus heteroclitus from a creosote-contaminated site. , 1990, Cancer research.

[168]  C. Portt,et al.  Impact of Bleached Kraft Mill Effluent on Population Characteristics, Liver MFO Activity, and Serum Steroid Levels of a Lake Superior White Sucker (Catostomus commersoni) Population , 1991 .

[169]  Tommy Andersson,et al.  Effects of exposure to food contaminated with PBDE, PCN or PCB on reproduction, liver morphology and cytochrome P450 activity in the three-spined stickleback, Gasterosteus aculeatus , 1993 .

[170]  M. James,et al.  Cytochrome P450 monooxygenases in crustaceans. , 1989, Xenobiotica; the fate of foreign compounds in biological systems.

[171]  J. Hendricks,et al.  Mechanisms of anti-carcinogenesis: the distribution and metabolism of aflatoxin B1 in rainbow trout fed aroclor 1254. , 1986, Carcinogenesis.

[172]  C. Hogstrand.  Regulation of metallothionein in teleost fish during metal exposure , 1991 .

[173]  J. Lech,et al.  Hepatic effects of acrylamide in rainbow trout. , 1987, Toxicology and applied pharmacology.

[174]  S. Adams.  Status and use of biological indicators for evaluating the effects of stress on fish , 1990 .

[175]  J. W. Owens,et al.  Exposure of fish to biologically treated bleached‐kraft effluent. 1. Biochemical, physiological and pathological assessment of rocky mountain whitefish (prosopium williamsoni) and longnose sucker (catostomus catostomus) , 1994 .

[176]  J. Stegeman,et al.  Cytochrome P-450 Monooxygenase Systems in Aquatic Species: Carcinogen Metabolism and Biomarkers for Carcinogen and Pollutant Exposure , 1991 .

[177]  Michael Ashburner,et al.  Heat shock, from bacteria to man , 1982 .

[178]  R. Gupta,et al.  Natural environment surpasses polluted environment in inducing DNA damage in fish. , 1989, Carcinogenesis.

[179]  L. Viganò,et al.  Xenobiotic metabolizing enzymes in uninduced and induced rainbow trout (Oncorhynchus mykiss): Effects of diets and food deprivation , 1993 .

[180]  David B. Peakall,et al.  Biomarkers : research and application in the assessment of environmental health , 1993 .

[181]  T. Andersson,et al.  Influence of environmental temperature on the induction of xenobiotic metabolism by beta-naphthoflavone in rainbow trout, Salmo gairdneri. , 1985, Toxicology and applied pharmacology.

[182]  A. Goksøyr,et al.  Cytochrome P450 in seals: monooxygenase activities, immunochemical cross-reactions and response to phenobarbital treatment , 1992 .

[183]  J. McCarthy,et al.  Biological markers of environmental and ecological contamination: an overview. , 1992, Risk analysis : an official publication of the Society for Risk Analysis.

[184]  Michael J. Leaver,et al.  Induction of piscine metallothionein as a primary response to heavy metal pollutants: applicability of new sensitive molecular probes , 1992 .

[185]  B. Jansson,et al.  Biotransformation enzyme activities and PCDD/PCDF levels in pike caught in a Swedish Lake , 1992 .

[186]  A. Edwards,et al.  Hepatic microsomal mono-oxygenase activity in flounder Platichthys flesus from polluted sites in Langesundfjord and from mesocosms experimentally dosed with diesel oil and copper , 1988 .

[187]  L. Rhodes,et al.  Chemical pollutants in sediments and diseases of bottom-dwelling fish in Puget Sound, Washington , 1984 .

[188]  A. Rahimtula,et al.  Review and perspective on the use of mixed-function oxygenase enzymes in biological monitoring. , 1987, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[189]  P. Garrigues,et al.  Mixed-function oxygenase enzymes as tools for pollution monitoring: field studies on the French coast of the Mediterranean Sea. , 1991, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[190]  C. Walker,et al.  The monooxygenases of birds, reptiles and amphibians. , 1989, Xenobiotica; the fate of foreign compounds in biological systems.

[191]  A. Goksøyr,et al.  Environmental contaminants and biochemical responses in flatfish from the Hvaler Archipelago in Norway , 1991, Archives of environmental contamination and toxicology.

[192]  A. Goksøyr,et al.  Species characteristics of the hepatic xenobiotic and steroid biotransformation systems of two teleost fish, Atlantic cod (Gadus morhua) and rainbow trout (Salmo gairdneri). , 1987, Toxicology and applied pharmacology.

[193]  Ȧ. Larsson,et al.  Biotransformation enzyme activities and histopathology in rainbow trout, Salmo gairdneri, treated with cadmium , 1986 .

[194]  P. Namour,et al.  Ethoxyresorufin-O-deethylase induction in fish from a watershed exposed to a non-point source pollution of agricultural origin , 1993 .

[195]  D. Rice,et al.  Mixed-function oxidase-specific activity in wild and caged speckled sanddabs Citharichthys stigmaeus in Elkhorn Slough, Moss Landing Harbor and nearshore Monterey Bay, California. , 1994, Environmental pollution.

[196]  S. Focardi,et al.  Mixed-function oxidase activity and conjugating enzymes in two species of antarctic fish , 1989 .

[197]  M. Ashburner,et al.  The induction of gene activity in drosophila by heat shock , 1979, Cell.

[198]  J. Masfaraud,et al.  Use of the fish cytochrome P-450-dependent 7-ethylresorufin O-deethylase activity as a biochemical indicator of water pollution. Study of the liver and the kidney of male and female nase (Chondrostoma nasus) from the River Rhône. , 1990, The Science of the total environment.

[199]  M. T. Donato,et al.  A rapid and sensitive method for measuring monooxygenase activities in hepatocytes cultured in 96-well plates , 1992 .

[200]  R. Burdon,et al.  Heat shock and the heat shock proteins. , 1986, The Biochemical journal.

[201]  M. Leaver,et al.  Molecular studies of the phase II xenbiotic conjugative enzymes of marine pleuronectid flatfish , 1992 .

[202]  A. Goksøyr,et al.  The cytochrome P-450 system in fish, aquatic toxicology and environmental monitoring , 1992 .

[203]  O Hänninen,et al.  Extrahepatic xenobiotic metabolism in North-European Freshwater fish. , 1981, Comparative biochemistry and physiology. C: Comparative pharmacology.

[204]  J. Stegeman,et al.  The temporal relationships between P450E protein content, catalytic activity, and mRNA levels in the teleost Fundulus heteroclitus following treatment with beta-naphthoflavone. , 1989, Archives of biochemistry and biophysics.

[205]  A. Goksøyr,et al.  A semi-quantitative cytochrome P450IA1 ELISA: A simple method for studying the monooxygenase induction response in environmental monitoring and ecotoxicological testing of fish , 1991 .

[206]  J. Masfaraud,et al.  7-ethylresorufin O-deethylase activity and level of DNA-adducts in trout treated with benzo(a)pyrene , 1992 .

[207]  C. Pueyo,et al.  Biochemical Indicators of Oxidative Stress in Fish from Polluted Littoral Areas , 1993 .

[208]  D. Rice,et al.  Effects of organic contaminants on reproduction of the starry flounder Platichthys stellatus in San Francisco Bay , 1988 .

[209]  J. W. Owens,et al.  Fish populations and biomarker responses at a Canadian bleached kraft mill site , 1992 .

[210]  T. Andersson.  Sex differences in cytochrome P-450-dependent xenobiotic and steroid metabolism in the mature rainbow trout kidney. , 1990, The Journal of endocrinology.

[211]  J. Giesy,et al.  Characterization of the H4IIE rat hepatoma cell bioassay as a tool for assessing toxic potency of planar halogenated hydrocarbons in environmental samples , 1991 .

[212]  Ȧ. Larsson,et al.  Effects of pulp bleach plant effluents on hepatic xenobiotic biotransformation enzymes in fish: Laboratory and field studies , 1985 .

[213]  B. Sanders,et al.  Tissue-specific differences in accumulation of stress proteins in Mytilus edulis exposed to a range of copper concentrations. , 1994, Toxicology and applied pharmacology.

[214]  J. Hellou,et al.  Induction of mfo enzymes and production of bile metabolites in rainbow trout (Oncorhynchus mykiss) exposed to waste crankcase oil , 1993 .

[215]  J. Stegeman,et al.  Induced Cytochrome P4501A in Winter Flounder, Pleuronectes americanus, from Offshore and Coastal Sites , 1994 .

[216]  S. Safe.  Determination of 2,3,7,8-TCDD toxic equivalent factors (TEFs): support for the use of the in vitro AHH induction assay , 1987 .

[217]  J. Stegeman,et al.  Induced cytochrome P-450 in Fundulus heteroclitus associated with environmental contamination by polychlorinated biphenyls and polynuclear aromatic hydrocarbons , 1989 .

[218]  G. Schultz,et al.  Expression of a set of fish genes following heat or metal ion exposure. , 1982, The Journal of biological chemistry.

[219]  J. Stegeman.  Temperature Influence on Basal Activity and Induction of Mixed Function Oxygenase Activity in Fundulus heteroclitus , 1979 .

[220]  G. Ankley,et al.  Temperature compensation in the hepatic mixed-function oxidase system of bluegill. , 1985, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[221]  N. M. Price,et al.  Phytochelatin production by marine phytoplankton at low free metal ion concentrations: laboratory studies and field data from Massachusetts Bay. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[222]  G. Roesijadi.  The significance of low molecular weight, metallothionein-like proteins in marine invertebrates: Current status , 1981 .

[223]  W. E. Hawkins,et al.  Sequential expression of biomarkers in Bluegill Sunfish exposed to contaminated sediment , 1992, Ecotoxicology.

[224]  J. Stegeman,et al.  Interlaboratory comparison and optimization of hepatic microsomal ethoxyresorufin O‐deethylase activity in white sucker (Catostomus commersoni) exposed to bleached kraft pulp mill effluent , 1993 .

[225]  D. Buhler,et al.  Localization of cytochrome P-450 in the head and trunk kidney of rainbow trout (Salmo gairdneri). , 1988, Toxicology and applied pharmacology.

[226]  P. Thomas.  Reproductive endocrine function in female atlantic croaker exposed to pollutants , 1988 .

[227]  W. L. Lockhart,et al.  Dietary accumulation and sustained hepatic mixed function oxidase enzyme induction by 2,3,4,7,8‐pentachlorodibenzofuran in rainbow trout , 1990 .

[228]  D. Livingstone.  Biotechnology and pollution monitoring: Use of molecular biomarkers in the aquatic environment , 1993 .

[229]  J. Stegeman,et al.  Polychlorinated biphenyls concentration and cytochrome P-450E expression in winter flounder from contaminated environments , 1989 .

[230]  S. De Flora,et al.  Metabolic and genetic effects of marine pollution on aquatic organisms. , 1991, Progress in clinical and biological research.

[231]  J. Lech,et al.  Caged and wild fish: Induction of hepatic cytochrome P‐450 (CYP1A1) as an environmental biomonitor , 1993 .

[232]  R. E. Wolke,et al.  Epizootic Carcinoma in the Winter Flounder, Pseudopleuronectes americanus , 1985, Science.

[233]  C. Portt,et al.  Changes in Maturity, Plasma Sex Steroid Levels, Hepatic Mixed-Function Oxygenase Activity, and the Presence of External Lesions in Lake Whitefish (Coregonus clupeaformis) Exposed to Bleached Kraft Mill Effluent , 1992 .

[234]  L. Hightower.  Cultured animal cells exposed to amino acid analogues or puromycin rapidly synthesize several polypeptides , 1980, Journal of cellular physiology.

[235]  A. Wiseman,et al.  Cytochrome P-450 and oxidative metabolism in molluscs. , 1989, Xenobiotica; the fate of foreign compounds in biological systems.

[236]  C. Ramachandran,et al.  Estrogenic regulation of uterine 90-kilodalton heat shock protein. , 1988, Endocrinology.

[237]  C. Metcalfe,et al.  Relative induction of aryl hydrocarbon hydroxylase by 2,3,7,8‐TCDD and two coplanar PCBs in rainbow trout (oncorhynchus mykiss) , 1991 .

[238]  W. L. Lockhart,et al.  Applications of hepatic mixed function oxidase enzyme activities to Northern freshwater fish: I. Burbot, Lota lota , 1992 .

[239]  P. R. Montellano.  Oxygen Activation and Transfer , 1986 .

[240]  R. Carlson,et al.  Hepatic mixed-function oxidase activity in rainbow trout exposed to several polycyclic aromatic compounds. , 1978, Environmental research.

[241]  H. Prosser,et al.  An investigation of the genotoxic effects of an organotin antifouling compound (Bis(tributyltin) oxide) on the chromosomes of the edible mussel, Mytilus edulis , 1986 .

[242]  T. T. Chen,et al.  Two unique CYP1 genes are expressed in response to 3-methylcholanthrene treatment in rainbow trout. , 1994, Archives of biochemistry and biophysics.

[243]  R. Spies,et al.  Hepatic mixed-function oxidases in California flatfishes are increased in contaminated environments and by oil and PCB ingestion , 1982 .

[244]  J. Beauchamp,et al.  The mixed function oxidase system of bluegill sunfish, Lepomis macrochirus: Correlation of activities in experimental and wild fish , 1988 .

[245]  D. Rice,et al.  Effects of organic contaminants on reproduction of the starry flounder Platichthys stellatus in San Francisco Bay , 1988 .

[246]  Tommy Andersson,et al.  Regulation of the cytochrome P450 enzyme system in fish , 1992 .

[247]  A. Oikari,et al.  Biotransformation activities of feral fish in waters receiving bleached pulp mill effluents , 1990 .

[248]  Paul D. Jones,et al.  Bioassay-Derived 2,3,7,8-Tetrachlorodibenzo-p-dioxin Equivalents in PCB-Containing Extracts from the Flesh and Eggs of Lake Michigan Chinook Salmon (Oncorhynchus tsha wyfscha) and Possible Implications for Reproduction , 1991 .

[249]  D. Siebers,et al.  Induction of the hepatic biotransformation system of golden ide [Leuciscus idus (L.)] after exposure in the River Elbe. , 1994, Ecotoxicology and environmental safety.

[250]  J. Stegeman.  Nomenclature for hydrocarbon-inducible cytochrome P450 in fish , 1992 .

[251]  J. Stegeman,et al.  Apparent cytochrome P-450 induction as an indication of exposure to environmental chemicals the flounder Platichthys flesus , 1988 .

[252]  S. De Flora,et al.  Multiple genotoxicity biomarkers in fish exposed in situ to polluted river water. , 1993, Mutation research.

[253]  J. Kägi,et al.  Chemistry and biochemistry of metallothionein. , 1987, Experientia. Supplementum.

[254]  A. Matin,et al.  Unique and overlapping pollutant stress proteins of Escherichia coli , 1992, Applied and environmental microbiology.

[255]  J. Whitlock,et al.  Mechanistic aspects of dioxin action. , 1993, Chemical research in toxicology.

[256]  A. Brouwer,et al.  Biochemical and toxic effects of polychlorinated biphenyls (PCBs), dibenzo-P-dioxins (PCDDs) and dibenzofurans (PCDFs) in the cormorant (phalacrocorax carbo) after in ovo exposure , 1994 .

[257]  J. J. Black,et al.  32P-postlabeling analysis of aromatic DNA adducts in fish from polluted areas. , 1987, Cancer research.

[258]  P. Hodson,et al.  Effects of bleached kraft mill effluent on fish in the St. Maurice River, Quebec , 1992 .

[259]  J. Stegeman,et al.  Endogenously-mediated, pretranslational suppression of cytochrome P4501A in PCB-contaminated flounder , 1992 .

[260]  L. Johnson,et al.  Contaminant Effects on Ovarian Development in English Sole (Parophrys vetulus) from Puget Sound, Washington , 1988 .

[261]  M. James,et al.  Polycyclic aromatic hydrocarbon induction of cytochrome P-450-dependent mixed-function oxidases in marine fish. , 1980, Toxicology and applied pharmacology.

[262]  H. Lipp,et al.  Induction of hepatic P450-dependent monooxygenase in feral mice from a PCDD/PCDF-contaminated area , 1991 .

[263]  Richard F. Lee,et al.  Responses of cytochromeP-450 systems in marine crab and polychaetes to organic pollutants , 1981 .

[264]  T. Collier,et al.  Hepatic activities of xenobiotic metabolizing enzymes and biliary levels of xenobiotics in english sole (Parophrys vetulus) exposed to environmental contaminants , 1991, Archives of environmental contamination and toxicology.

[265]  J. Stegeman,et al.  Induced Cytochrome P450 in Winter Flounder (Pseudopleuronectes americanus) from Coastal Massachusetts Evaluated by Catalytic Assay and Monoclonal Antibody Probes , 1987 .

[266]  J. W. Owens,et al.  Environmental biomarkers as indicators of chemical exposure , 1993 .

[267]  Mark S. Myers,et al.  Neoplastic and other diseases in fish in relation to toxic chemicals: an overview☆ , 1988 .