A QUANTITATIVE CYTOCHEMICAL STUDY ON THE PATHOGENESIS OF STREPTOZOTOCIN-INDUCED EPITHELIAL TUMORS IN RAT-KIDNEY

We investigated the development of early neoplastic lesions preceding the appearance of kidney epithelial tumors in rats treated with a sing le iv injection of 35 mg/kg of streptozotocin (STZ). Most of these les ions were associated with segments of atrophied and regenerative nephr ons surrounded by a thick basal membrane that appear precociously in c hronic progressive nephropathy. Cytochemical periodic acid-Schiff, Alc ian blue, and colloidal iron reactions did not indicate an excessive s torage of glycogen or acid mucopolysaccharides in early neoplastic les ions and tumors. Quantitative cytochemistry of mitochondrial succinate , alpha-glycerophosphate, and reduced nicotinamide adenine dinucleotid e-dehydrogenases revealed a shift in metabolism toward glycolysis in a trophied and regenerative nephrons as well as in early neoplastic lesi ons and tumors. These correlative cytomorphological and cytochemical f indings raise the possibility that changes associated with the initial stages of chronic progressive nephrosis may provide favorable conditi ons for the selective growth of STZ-initiated cells that generate foca l collections of proliferating cells and then progress to tumor growth . Tumor prevalence was remarkably constant in animals sacrificed 33, 4 8, and 54 wk after treatment, suggesting that the prominent inflammato ry and scarring reaction later developing in the course of progressive nephrosis might contribute to control the growth of STZ-induced cance r.