Toxicity of TCDD in European flounder (Platichthys flesus) with emphasis on histopathology and cytochrome P450 1A induction in several organ systems

The present study is part of a series of experiments. set up to elucidate t he impact of aquatic pollution on fish health in the marine and estuarine e nvironment. In the Dutch coastal and estuarine waters. European flounder (P latichthys flesus) showed a relatively high prevalence of (pre)neoplastic l iver lesions and lymphocystis virus disease. The hypothesis of a causal rel ationship between pollution and these diseases was supported by semi-field experiments. Therefore a series of laboratory experiments was performed to further substantiate causality and identify the xenobiotics that may play a major role in the field. Polychlorinated dibenzo-p-dioxins (PCDDs) and dib enzofurans (PCDFs) are important environmental pollutants. They are highly persistent. highly lipophilic, and have shown to induce several toxic effec ts ill mammalian and non-mammalian species at relatively low concentrations . This report describes a study in which European flounder were orally expo sed to the most toxic PCDD congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (T CDD) or to harbor sludge extract under controlled laboratory conditions. Th e effects on several organs (liver. gills, gastro-intestinal tract, thyroid gland, gonads, spleen and mesonephros) were examined microscopically. Indu ction and localization of cytochrome P4501A (CYP1A) immunoreactivity and ef fects on hepatocyte-proliferation were visualized immunohistochemically. Ef fects on thymus size were examined by morphometric analysis. Oral exposure of flounder to 0.0125 or 0.3125 mu g TCDD/kg bw, or to 0.3125 mu g TEQ/kg b w of a harbor sludge extract, weekly for 8 weeks, induced a significant inc rease in CYP1A immunoreactivity in hepatocytes. Single administration of hi gher doses (20, 100 and 500 mu g/kg bw) of TCDD also induced a significant increase CYP1A immunoreactivity in the endothelium in all organs examined, and in the epithelium of the digestive tract, liver. and mesonephros. Remar kably, strong immunoreactivity was noted in a distinct cell population of t he hematopoietic tissue In the mesonephros and spleen. which haj not been d escribed in fish previously. Moreover, oral exposure to 20 mu gTCDD/kg bw r esulted in an increased mitotic activity, and an increased hepatosomatic in dex was found after exposure to 500 mu gTCDD/kg bw. In the thymus only a tr end in size reduction was noted, again in the highest dose group. Neverthel ess, no marked pathology was detected even in fish exposed to a single dose of 500 mu g TCDD/kg body weight. The present experiments show that, under the actual experimental conditions, European flounder is relatively insensi tive to the toxic effects of TCDD. However, we assume that exposure to TCDD (and related substances) may promote the development of tumors in the fiel d. (C) 2401 Elsevier Science B.V. All rights reserved.