Application of scanning electron microscopy and X-ray analysis to urinary tract cancer in animals and humans

Scanning electron microscopy (SEM) has proven useful in various aspects of urinary bladder carcinogenesis research and these are reviewed as they pertain to our research involving sodium saccharin in the rat. Sodium saccharin-carcinogenesis in rats requires administration at high doses beginning at birth or earlier. Administration beginning at ages of 5 weeks or later results in much lower incidences of bladder tumors. Methods were developed for examining the rat fetal and neonatal bladder to further evaluate effects at these critical ages. Several significant differences were found by SEM between the fetal bladder compared to the adult. The typical polygonal superficial cells of the bladder with asymmetric unit membrane were present before birth, but the slow turnover rate of the adult bladder did not occur until 3-4 weeks of age. Sodium saccharin causes increased proliferation rates and hyperplasia of the urothelium which is dose-dependent. SEM was found to be more sensitive than either light microscopy or labeling indices to detect the earliest lesions induced by sodium saccharin. More recently, amorphous and crystalline material in the urine of rats fed high doses of sodium saccharin were detected by SEM examinations which contained silicon as well as calcium, phosphate, and magnesium as detected by energy dispersive X-ray analysis (EDS) with the SEM. These parameters may be relevant to differences between rats and humans and pertain to extrapolations regarding risk assessment.