|
(331) Lysosomes in toxic injury and carcinogenesis of the liver of marine flatfish: an immuno histochemical study. Köhler, Angela1, Bahns, Sieglinde 1, Broeg, Katja 1, Lauritzen, Bjarne1, 1 ABSTRACT- Flounder (</Platichthys flesus L.>) were sampled along a pollution gradient in the German Wadden Sea for histological diagnosis of liver lesions, simultaneous immuno and enzyme histochemical analysis of lysosomal changes as well as for analytical chemistry in same livers for organochlorines and heavy metals. Lysosomal perturbations were detected by the latency test, neutral lipid accumulation (Oil Red O) and their size in hepatocytes while in liver macrophages acid phosphatase and G6PDH enzyme activity and protein expression was used, additionally, to determine functional integrity and activity in this type of immune cells. The aim of our interdisciplinary approach was to analyse whether lysosomal changes in liver cells of fish reflect progression of toxically induced liver pathologies and respond to the accumulation of contaminants. Lysosomal membrane stability was disrupted with the onset of liver anomalies and persisted in degenerated livers, and in extralesional parenchyma during carcinogenesis. But, in hepatocellular carcinomas highest values of membrane stability were detected in small numerous lysosomes in proliferating cancer cells. Macrophages showed a temporary increased activity in reversibly damaged livers which decreased again in liver degeneration and were further deactivated in a gradient-like manner in the vicinity of malignant carcinomas. Levels of organochlorines were positively correlated with intralysosomal accumulation of neutral lipids while heavy metals showed negative correlations. Interlinking of contaminant levels to lysosomal latency evidenced that highest levels of certain organochlorines such as HCH-isomers, DDT metabolites and PCB congeners in the liver coincided with highly significant reduction of lysosomal latency while in livers with low contaminant concentrations we observed a high lysosomal membrane stability. biomarkers of toxic effects. Lysosomal changes could be used as rapid tool to identify tocically caused liver dysfunction in early liver injury while in carcinogenesis we recommend the parallel use of H&E stained sections for the localisation of foci and tumors to avoid misinterpreation of lysosomal responses. Key words: biomonitoring, flatfish liver, lysosomes, carcinogenesis |
