Toxicity of PCB-126 in European flounder (Platichthys flesus) with emphasis on histopathology and cytochrome P4501A induction in several organ systems

A series of experiments was set up to elucidate the effects of pollution on marine and estuarine fish health, since the European flounder (Plalichthys flesus) has shown a relatively high prevalence of (pre:)neoplastic liver l esions and lymphocystis virus disease in dutch coastal and estuarine waters . The hypothesis of a causal relationship between pollution and the above-m entioned diseases was supported by results from semi-held experiments. Ther efore several laboratory experiments were carried out to substantiate causa lity further and to identify the xenobiotics that may play a major role in the field. The present study focuses on polychlorinated biphenyls (PCBs). E uropean flounders (Platichthys flesus) were orally exposed to a single dose of 0, 0.5, 5 or 50 mg PCB-126/kg body weight under controlled laboratory c onditions. The effects on liver, gills, gastrointestinal tract, gonads, spl een and mesonephros M ere examined histologically after 16 days. Induction and localization of cytochrome P4501A (CYP1A) immunoreactivity, and effects on hepatocyte proliferation were visualized immunohistochemically. Effects on thymus size were examined by morphometric analysis of serial sections, Three out of five animals of the highest dose group showed haemorrhages in the fins and tail after 16 days. All animals showed reduced activity in the later stages of the experiment: and some animals of the highest dose group discontinued feeding 14 days after exposure. Strong and exposure-related i nduction of CYP1A immunoreactivity was noted in hepatocytes, endothelium in all organs examined, and epithelium of the digestive tract and mesonephros at PCB-126 levels of 0.5, 5 and 50 mg/kg. In addition. the strong inductio n of CYP1A immunoreactivity in a distinct population of haematopoietic cell s in the mesonephros and in circulating bleed is remarkable, and has not be en described previously in other fish species. Furthermore. a morphometrica lly determined significant reduction in relative thymus size was noted in a nimals exposed to 50 mg PCB-126/kg. Although the functional implications fo r the immune system of this reduction need to be further investigated, an i mpact on the specific resistance against infectious diseases as observed in the field. e.g. viral lymphocystis disease, is not implausible. In additio n, a significant increase in absolute liver weight, in hepatosomatic index, and in number of proliferating hepatocytes [measured as immunoreactivity a gainst proliferating cell nuclear antigen (PCNA)I was noted in animals of t he highest dose group, From these findings we suppose that PCB-126 (and rel ated chemicals) may play a role in the promotion of tumour development in t he liver of European flounders as observed ill the field, The results of th e present experiment show relatively stronger effects than effects previous ly reported from experiments with TCDD, suggesting that the TEF of 0.005 as signed to PCB-126 from early life stage mortality experiments in rainbow tr out (Oncorhynghus mykiss), underestimates the toxic potential of PCB-126.