Effect of sodium saccharin on the neonatal rat bladder.
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
S M
SM
University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha, Nebraska, 68198, USA.
Cano
M
M
St John
M K
MK
Garland
E M
EM
Khachab
M
M
Ellwein
L B
LB
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006965:Hyperplasia; D008297:Male; D008855:Microscopy, Electron, Scanning; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012439:Saccharin / Q000633:toxicity*; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure
D002273:Carcinogens; D004247:DNA; D012439:Saccharin