INITIAL VELOCITIES IN-SITU OF G6PDH AND PGDH AND EXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) - SENSITIVE DIAGNOSTIC MARKERS OF ENVIRONMENTALLY-INDUCED HEPATOCELLULAR CARCINOGENESIS IN A MARINE FLATFISH (PLATICHTHYS-FLESUS L)

Flounder (Platichthys flesus L.) were sampled in areas of relatively l ow contamination, in the open sea, and in a region at the mouth of the highly contaminated river Elbe (Germany). Prognostic and diagnostic v alues of the in situ reaction velocities of glucose 6-phosphate dehydr ogenase (G6PDH) and phosphogluconate dehydrogenase (PGDH) inside and o utside altered hepatocellular foci and carcinomas were demonstrated hi stochemically. Reactions were monitored quantitatively in time using i mage analysis. Expression of proliferating cell nuclear antigen (PCNA) was detected in serial sections as a marker for cell proliferation us ing the immunogold-silver labelling technique. Enzymic parameters were correlated with PCNA expression and histopathology. A large variety o f foci and tumours were found in the livers of fish from the contamina ted area. Histopathological classification could only indicate tendenc ies with respect to diagnosis and prognosis. However, in all stages of carcinogenesis, from early foci to well-organized trabecular basophil ic tumours and anaplastic carcinomas, significantly higher initial vel ocities of G6PDH but not of PGDH and a higher PCNA labelling index (43 -65%) were found in altered hepatocytes in comparison with surrounding extrafocal tissue. Furthermore, the increased capacities of G6PDH and PGDH in basophilic foci and nodules were found to be useful prognosti c parameters. Significantly increased PCNA expression in small satelli tes of carcinomas reflected their malignancy and was used to different iate between early foci and invasive protrusions of carcinomas. It is concluded that G6PDH activity and PCNA expression are very useful as d iagnostic and prognostic tools to detect early preneoplastic lesions a nd to analyse progression towards carcinomas in environmental monitori ng. (C) 1998 Elsevier Science B.V.