In a two-generation bioassay, high doses of dietary sodium saccharin (NaSac) produce bladder carcinoma in rats, whereas acid saccharin (HSac) does not effect the urothelium. NaSac and HSac administered as 5% of the diet to F0 Sprague-Dawley (SD) and F344 rats, continued through to the weaned male rats for ten additional weeks. Control 3H-thymidine labeling index (LI) was high prior to and at birth (approximately 11%), declining rapidly by weaning (to < 0.2). Neither NaSac nor HSac increased proliferation through 7 days of age. NaSac increased the proliferation rate at later times, whereas HSac did not. The LI decreased to control levels in NaSac-fed rats switched to control diet after weaning and increased in control-fed rats switched to NaSac after birth or weaning. In a second experiment, 5% NaSac did not affect urothelial morphology of SD rats through 7 days. By 21 days post-birth, urothelial hyperplasia occurred in NaSac-fed rat. The LI in treated versus control was similar through gestation, with a slight difference by 7 days. LI was significantly different by 21 days post-birth, but was similar between males and females. These results provide additional evidence for the increased cell proliferative effects of NaSac during the neonatal period, but not during gestation.
Cohen, Samuel M.; Cano, Martin; St. John, Margaret K.; Garland, Emily M.; Khachab, Mohamad; and Ellwein, Leon B.
"Effect of Sodium Saccharin on the Neonatal Rat Bladder,"
Scanning Microscopy: Vol. 9
, Article 9.
Available at: https://digitalcommons.usu.edu/microscopy/vol9/iss1/9