Study of sodium saccharin co-carcinogenicity in the rat.
A co-carcinogenicity experiment was conducted with female Sprague-Dawley rats in which the effects of short-term sodium saccharin dosing and initiation with a direct-acting carcinogen were examined in the urinary bladder. All initiated animals were administered 0.5 mg N-methyl-N-nitrosourea (MNU) by instillation into the bladder at 8 wk of age. The animals were also given saccharin at one of four levels in the diet (0, 1.0, 2.5 or 5%) for 4 wk either (1) just before treatment with MNU (4-8 wk of age), (2) centred on treatment with MNU (6-10 wk of age) or (3) after MNU treatment (8-12 wk of age). Additionally, a group of animals was exposed to saccharin through the milk for 3 wk by dosing the mothers, starting on the day of parturition. The animals were held on control diet until interim killing of 20 animals per group at about 590 days of age, removal for morbidity, or terminal killing of the remainder of 60 animals per treatment around 780 days of age. A histopathological examination was made of the urinary tract and the relationship of saccharin dose to bladder tumour prevalence analysed statistically. A consistent increase (with very weak statistical significance) in tumour rate at interim killing, and for the pathology data overall, was shown by the 2.5% dose group given saccharin from 8 to 12 wk of age. Tumour prevalences of 47.6 and 40.7% v. control prevalences of 21.1 and 25.4% were observed for the two time periods (P values < 0.076 and < 0.0853, respectively). All groups given saccharin neonatally showed increased tumour prevalence for both time periods, but none of the differences was statistically significant at the 95% confidence level. No consistent increase in tumour prevalence was seen in the groups given saccharin from 4 to 8 or 6 to 10 wk of age; thus, these data suggest that saccharin does not act as a strong co-carcinogen in the MNU-treated rat bladder.
West
R W
RW
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Sheldon
W G
WG
Gaylor
D W
DW
Allen
R R
RR
Kadlubar
F F
FF
D000818:Animals; D015197:Carcinogenicity Tests; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced* / Q000473:pathology; D003043:Cocarcinogenesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012439:Saccharin / Q000008:administration & dosage / Q000633:toxicity*; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology
D008770:Methylnitrosourea; D012439:Saccharin