title: Toxicology of environmental chemicals in the flounder (Platichthys flesus) with emphasis on the immune system: field, semi-field (mesocosm) and laboratory studies.
abstract: European flounder (Platichthys flesus) has shown an increased prevalence of liver tumors and lymphocystis disease (a viral infection) that correlated with pollution in field research in Dutch coastal and estuarine waters. Semi-field or mesocosm experiments confirmed the supposed causality. Although these types of research are highly relevant for the feral population, laboratory experiments are necessary to establish causal relationships between specific chemical pollutants and disease. Therefore, the effects on flounder of some of the potentially causative chemicals such as benzo[a]pyrene (BaP), dimethyl-benz[a]anthracene (DMBA), 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5 pentachlorobiphenyl (PCB-126), and bis(tri-n-butyltin)oxide (TBTO) were examined in several laboratory experiments. These effects were evaluated using general toxicological parameters and histopathology. For immune function assessment, attempts to develop an infection model with the lymphocystis virus were made, but appeared unsuccessful and immune function tests are not fully operational at the moment. Flounder has been successfully maintained and exposed to toxic substances in captivity in our laboratory. Short-term aqueous exposure to high levels of BaP or DMBA did not induce marked effects under our experimental conditions. Results of oral exposure of flounder to low levels of TCDD, PCB-126 or harbor sludge extract show significant induction of cytochrome P4501A (CYP1A) in hepatocytes. Oral exposure to high levels of TCDD or PCB-126 also significantly induced CYP1A immunoreactivity in epithelium in mesonephros and digestive tract and in endothelium in several organs. Remarkable was the induction of CYP1A in a distinct population of mononuclear cells in the mesonephros. Moreover, oral exposure to TCDD resulted in an increased mitotic activity and an increase of the hepatosomatic index in the 20 and 500 microgram TCDD/kg group respectively. Therefore, exposure to TCDD and related substances may promote the development of liver tumors in the field. Exposure to PCB-126 also significantly reduced the relative thymus volume, but other results indicate that flounder is relatively insensitive to this type of chemicals. Short-term aqueous exposure of flounder to TBTO, in concentrations that were in the same order of magnitude as upper TBT levels measured in the field, caused mortality after 7-12 days associated with gill lesions, and induced reduction of the non-specific resistance and decrease of the relative thymus volume. From these results we therefore conclude that TBTO might play a causal role in, for instance, increased prevalence of lymphocystis virus infections in the field
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Utrecht University, NL-3508 TD, Utrecht, The Netherlands. g.grinwis@pobox.uu.nl
authors.forename: G C
authors.initials: GC
authors.lastname: Grinwis
authors.forename: A D
authors.initials: AD
authors.lastname: Vethaak
authors.forename: P W
authors.initials: PW
authors.lastname: Wester
authors.forename: J G
authors.initials: JG
authors.lastname: Vos
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity*; D005432:Flounder / Q000276:immunology; D007107:Immune System / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D012623:Seawater; D012989:Soil Pollutants / Q000633:toxicity; D013154:Spleen / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D002274:Carcinogens, Environmental; D012989:Soil Pollutants; D014874:Water Pollutants, Chemical