A Quantitative Cytochemical Study on the Pathogenesis of Streptozotocin-Induced Epithelial Tumors in Rat Kidney

Abstract

We investigated the development of early neoplastic lesions preceding the appearance of kidney epithelial tumors in rats treated with a single iv injection of 35 mg/kg of streptozotocin (STZ). Most of these lesions were associated with segments of atrophied and regenerative nephrons surrounded by a thick basal membrane that appear precociously in chronic progressive nephropathy. Cytochemical periodic acid-Schiff, Alcian blue, and colloidal iron reactions did not indicate an excessive storage of glycogen or acid mucopolysaccharides in early neoplastic lesions and tumors. Quantitative cytochemistry of mitochondrial succinate, α-glycerophosphate, and reduced nicotinamide adenine dinucleotide—dehydrogenases revealed a shift in metabolism toward glycolysis in atrophied and regenerative nephrons as well as in early neoplastic lesions and tumors. These correlative cytomorphological and cytochemical findings raise the possibility that changes associated with the initial stages of chronic progressive nephrosis may provide favorable conditions for the selective growth of STZ-initiated cells that generate focal collections of proliferating cells and then progress to tumor growth. Tumor prevalence was remarkably constant in animals sacrificed 33, 48, and 54 wk after treatment, suggesting that the prominent inflammatory and scarring reaction later developing in the course of progressive nephrosis might contribute to control the growth of STZ-induced cancer.