Diseases of flounder Platichthys flesus in Dutchcoastal and estuarine waters, with particular reference to environmental stress factors. were diagnosed as hepatocellular carcinoma. Most of the remaining nodules were diagnosed as foci of cellular alteration, whlch are considered to be preneoplastic lesions. Routine histopathological examination of livers showing no gross pathology resulted in the identification of a range of lesions including hepatocellular adenoma, foci of cellular alteration, hydropic vacuolization of biliary epithelial cells and hepatocytes, inflammatory lesions, focal necrosis, regenerative foci, and fibrillar hepatocytes of unknown significance. In addition, indices were used to quantify the presence of storage vacuoles (glycogen and lipid) and the relative density of melanomacrophage centres. The results indicate that a small proportion of neoplasms would be missed if only livers with grossly detectable nodules were subjected to histological examination. The prevalence of foci of cellular alteration at the different sampling sites showed a good correspondence with that of neoplasms, providing support for the hypothesis that these conditions represent stages of the same process. Of the other lesions and quantitative ~ndices, only hydropic vacuolization of billary epithelia] cells had a spatial distribution similar to that of neoplasms. 11 is concluded that liver neoplasms and especially their precursor lesions in flounder are promising tools for monitoring exposure to potential carcinogens, provided that migration patterns are explicitly taken into account. Furthermore, experimental studies are needed to investigate the chemical agents responsible for the onset of these early lesions and their progression into neoplasms, and also to evaluate the contribution of other environmental and host-related factors. Liver histopathology
Diseases of flounderFlounder were found to be affected by the viral skin disease lymphocystis and by skin ulcers probably of bacterial origin. Overall prevalences of these 2 diseases in fish 2 2 yr old were 14.3%r and 2.8% respectively. Also notable was t h e presence of neoplastic nodules in the livers of 1.0% of the population, prevalences rising steeply with a g e and locally attaining values of up to 3 0 % in 6+ yr old fish. Most of the samples were collected in September when flounder are resident in inshore feeding arcas. Using data from 9 sites, spatial and temporal (year-to-year) variation in disease occurrence was analysed statistically using log-linear models which incorporated possible effects of length, a g e and sex. Year-toyear variation showed little correspondence among the 3 diseases, but their spatial distributions showed striking similarities. Lymphocystis and skin ulcers were associated in individual fish. The observed variation in disease prevalence showed no significant correlation with condition factor of the fish or with concentrations of contaminants in sediments or tissues. However, disease preval e n c e~ at different sites showed a strong positive correlation with fishing activity (possibly indicating an effect of damage by fishing gear) and appeared also to be positively related to salinity. When only strictly marine sites were considered, a relationship with pollution could not be ruled out. Additional data collected in February-April at offshore sites indicated that disease preval e n c e~ were generally higher at this time of the year, which corresponds to the spawning period of the populations studied. This trend was particularly pronounced for liver neoplasms, and might be partly related to a low condition factor resulting from spawning activities. In view of the different aetiologies of the 3 diseases, the similarities in spatial patterns indicate the existence of 1 general underlying mechanism of disease causation, perhaps acting through immunosuppressive effects. However, age-related migration appeared to explaln some aspects of the spatial pattern of liver neoplasms, whereas it was less important in the case of epidermal diseases, which develop more rapidly. On the basis of the findings of this study, the possible contribution of pollution to disease prevalence cannot be adequately assessed due to the interfering effects of other factors (salinity, fishing activity, migration and spawning). Disease causation appears to be con~plex, and it may be that effects of pollution interact with those of other factors to produce observed, spatial patterns.
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