Influences of Diet and Strain on the Proliferative Effect on the Rat Urinary Bladder Induced by Sodium Saccharin

Rats were fed sodium saccharin as 5 or 7.5% of the diet by weight, and proliferation of the bladder epithelium was assessed by autoradiography, histology, and scanning electron microscopy. In Experiment 1, male F344 rats, 5 weeks old, were placed on a diet of 0, 5, or 7.5% NaS mixed in Prolab 3200, NIH-07, or AIN-76A diet for 4 or 10 weeks. In Experiment 2,5-week-old F344 rats or 4-week-old Sprague-Dawley rats were fed 0, 5, or 7.5% NaS in Prolab 3200 or Purina 5002 diet for 10 weeks. In Experiment 1, at both the 4- and 10-week intervals, NaS had a greater effect on the urothelium when administered in the Prolab diet compared to the NIH diet, and there was little response with the AIN diet. Eight of 10 rats fed 7.5% NaS in Prolab 3200 for 4 or 10 weeks had bladders with simple or nodular hyperplasia, and eight of nine bladders contained abnormal surface features visible by scanning electron microscopy. At 10 weeks for control animals, the average labeling index following [ 3 H]thymidine incorporation into bladder epithelium was ~0.05%. For rats fed 7.5% NaS diets, the labeling index was 0.43% for Prolab, 0.14% for NIH-07, and 0.04% for AIN-76A. In Experiment 2, the response to NaS was considerably greater in F344 rats than in Sprague-Dawley rats fed the same diet, and for both strains, the response to NaS was greater in Prolab than in Purina diets. In conclusion, the proliferative effect of NaS on male rat urinary bladder depended on rat strain as well as on type of diet.