Cellular changes in rat urinary bladder carcinomas induced by FANFT: A quantitative electron microscopic analysis

Morphometric data of normal and neoplastic urinary bladder epithelia have been collected from the Fischer rat FANFT model. Sequential measurements of volumes, surface areas, and numerical densities of organelles, and where pertinent, cellular compartments have been made during FANFT carcinogenesis, utilizing standard point and intersection counting methods. The data show that neoplastic transformation of rat bladder epithelium, and progression of FANFT tumors are associated with increasing volume densities of cells, nuclei, microvilli, rough endoplasmic reticulum, and mitochondria, as well as with decreasing volume densities of the cytoplasmic matrix, fusiform vesicles, Golgi complex, and lysosomes. Surface densities of the plasma membrane (microvillar), nuclei, rough endoplasmic reticulum, as well as mitochondrial outer and inner membranes progressively increase while surface densities of non-microvillar plasma membrane, fusiform vesicles, and Golgi complex decrease with time. Smooth endoplasmic reticulum reaches its maximum volume and surface densities in tumors present 26 weeks after the initiation of FANFT feedings (26-F tumors). This may reflect the function of smooth endoplasmic reticulum as the site of detoxification of the carcinogen, noting that FANFT is metabolized by microsomal enzymes, and in this experiment is fed only for 26 weeks. The nuclear/cytoplasmic ratio is 1:4 in normal Fischer rat urothelium, 1:3 in 26-F and 43-F tumors, which are noninvasive, and 1:2 in 61-F, which are invasive tumors. The quantitative data correlate well with the changes in degree of differentiation of the tumors and with their biological behavior.