Mitochondrial anomalies in renal oncocytes induced in rat by N-nitrosomorpholine

Renal oncocytes were induced in male Sprague-Dawley rats by oral application of N-nitrosomorpholine (NNM) in a concentration of 12 or 50 mg per 100 ml drinking water and analysed by transmission electron microscopy. The oncocytes exhibited mitochondrial anomalies which were very similar to those of human oncocytoma oncocytes. The most striking mitochondrial changes were an unusually large number of the organelles and an excess of the cristae mitochondriales. The shape of the mitochondria varied from round and oval to extremely elongated slender or cup-shaped organelles often piled up to form complex bodies. Rarely large ramifying mitochondria were found. In addition to transversely orientated cristae or tubules the inner mitochondrial membranes frequently formed dense stacks of unusually long cristae often arranged longitudinally. In some mitochondria straight and strictly parallelly arranged neighbouring cristae were found to be connected by a paracrystalline array of pillars bridging the mitochondrial matrix. In the majority of oncocytes the mitochondrial matrix contained prominent dense granules (diameter 30-50 nm), but sometimes these were rare or absent. Individual mitochondria of many oncocytes showed membrane-bound deposits of glycogen particles which usually formed rosettes (alpha-particles) with a diameter of about 80 nm. Partitioned mitochondria were not seen. Often autophagic vacuoles containing portions of degraded mitochondria and dense bodies, probably autophagosomes, were observed. The nature and significance of the oncocytes remains unclear, but we suggest from these and earlier experimental results that oncocytes represent a special type of a neoplastically transformed cell which usually has only a low potential for "autonomous" growth. Renal oncocytes induced in rats by chemical carcinogens appear to be an excellent experimental model for the further investigation of this cell type.