Adenocarcinoma of the Kidney. II. Enzyme Histochemistry of Renal Adenocarcinomas Induced in Rats by N-(4′-Fluoro-4-biphenylyl)acetamide23

Abstract

Activities of a broad spectrum of enzymes were studied histochemically in renal adenocarcinomas induced in young male F344 rats by chronic dietary administration of the carcinogen N-(4′-fluoro-4-biphenylyl)acetamide. Enzymes included were: dehydrogenases of glucose-6-phosphate, lactate, succinate, malate, and a-glycerophosphate; peroxidase (catalase); glucose-6-phosphatase; alkaline and acid phosphatase; Mg²⁺ ATPase; 5′-nucleotidase; and aminopeptidase. Levels of enzyme activity were estimated visually and scored from 0 (not detectable) to a maximum of 5 (intense). Comparison of estimated activity for each enzyme was made between small neoplastic nodules (stage III tumors) and large adenocarcinomas (stage IV tumors) and between tumors and portions of normal proximal tubules in parenchyma of kidneys from untreated control rats. The results, which revealed nearly identical levels of activity for most enzymes In both stages III and IV tumors, suggested similar metabolic and biologic behavior of these lesions. However, when data for tumors were compared with data for normal proximal tubules, striking differences were observed consistent with: 1) a marked shift of energy metabolism from oxidative to glycolytic production of ATP, with a corresponding reduction in mitochondrial respiration; and 2) simplification of plasma membrane specializations that were possibly associated with a reduction or loss of transport function. These findings were compared with other histochemical, biochemical, and ultrastructural studies of renal adenocarcinomas in rats and man.