OVER-EXPRESSION OF GLUCOSE-TRANSPORTER ISOFORM GLUT1 AND HEXOKINASE-IIN RAT RENAL ONCOCYTIC TUBULES AND ONCOCYTOMAS

Renal oncocytomas, which have previously Introduction been shown to or iginate from the collecting duct system, were induced in male Sprague- Dawley rats by oral administration of N-nitrosomorpholine (NNM) for 7 weeks. The expression of glucose transporter isoforms GLUT1 and GLUT2, and of several enzymes involved in glucose metabolism [hexokinase (HK ), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydroge nase (MDH)] were studied by cytochemical approaches in serial cryostat sections of the kidney 12, 23 and 34 weeks after withdrawal of NNM. O ncocytic tubules connected with collecting ducts were first observed 2 3 weeks, and oncocytomas 34 weeks after withdrawal. The cytochemical p attern of oncocytic tubules and oncocytomas was similar, but differed markedly from that of normal collecting ducts in nearly all variables studied; expression of GLUT1 and hexokinase I proteins were strongly i ncreased; activities of HK, PK and MDH were elevated, while LDH activi ty was reduced. These results suggest that oncocytic transformation is associated with fundamental changes in energy metabolism which differ from those in cell lineages leading to other types of renal cell tumo urs, such as clear/acidophilic and basophilic cell tumours. The charac teristic over-expression of GLUT1 may be used as a diagnostic criterio n for the discrimination between oncocytes and acidophilic (granular) cells in clear/acidophilic renal cell tumours which show a reduced exp ression of this glucose transporter protein.