Functional and morphological changes of lysosomes as prognostic biomarkers of toxic liver injury in a marine flatfish (Platichthys flesus (L.))

Abstract

Lysosomes are cell organelles in which macromolecules are recycled and that protect cells against toxins. In the present study, we apply histopathological and histochemical techniques in parallel with analytical chemistry of organochlorines and heavy metals in livers, with and without histopathological lesions, of the flatfish Plathichthys flesus (L.). The fish were caught along a pollution gradient on the German North Sea coast. We analyze critically whether changes in morphology and function of lysosomes, reflecting the onset and progression of toxipathic lesions in the liver of flounder, are appropriate for the rapid application in biological-effect monitoring programs such as BEEP (European Union Project in the 5th Framework Biological Effects of Environmental Pollutants in Marine Coastal Ecosystems). Livers collected from wild flounder were graded into four categories of lesions. Lysosomal stability was plotted against progressive lesions and contaminant levels in the same livers. Lysosomal membrane stability was already decreased at the onset of liver anomalies that are regarded as reversible. Reduced membrane stability also persisted in degenerative liver lesions and during carcinogenesis in liver parenchyma surrounding foci and tumors. Decreased lysosomal membrane stability coincided with increased size of lysosomes and increased lipid content during the progression toward degeneration. As predicted by the resistant-cell hypothesis, in proliferating cancer cells of adenomas and carcinomas, the highest values of membrane stability were detected. Concentrations of organochlorines such as hexachlorcyclohexane isomers, DDT metabolites, and polychlorinated biphenyls were correlated with reduced lysosomal membrane stability in noncancerous hepatocytes. On the basis of these findings, we recommend applying the lysosomal membrane stability test as an expertise-independent and rapid prognostic biomarker for toxically induced liver injury and carcinogenesis in monitoring programs.