title: Lack of bladder tumor promoting activity in rats fed sodium saccharin in AIN-76A diet.
abstract: Sodium saccharin (NaSac) fed as 5% of Prolab diet promotes bladder tumor carcinogenesis in male F344 rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed as 0.2% of the diet for 4 weeks. NaSac also increases urothelial proliferation if fed for short periods in Prolab diet, but no increased proliferation is seen if it is fed for up to 10 weeks in AIN-76A semisynthetic diet, even at levels as high as 7.5% of the diet. To determine whether NaSac as part of an AIN-76A diet has promoting activity, groups of approximately 30 male, 5-week-old F344 rats were fed AIN-76A diet containing (a) 0.2% FANFT for 4 weeks followed by 5% NaSac for 100 weeks; (b) 0.2% FANFT followed by control diet; or (c) control diet followed by 5% NaSac. Bladder tumor incidences were 10, 23, and 0%, respectively. When fed in Prolab diet, 0.2% FANFT for 4 weeks followed by NaSac or control diet for 100 weeks resulted in bladder tumor incidences of 40 and 17%, respectively. Groups of rats fed 0.1 or 0.2% FANFT for 1 or 2 weeks followed by 5% NaSac or control diet for 100 weeks had bladder tumor incidences of 0 to 7%. These data demonstrate that NaSac does not promote bladder cancer in male rats if fed in AIN-76A diet. Other studies suggest that this is due to the low urinary pH in rats fed AIN-76A diet.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135.
authors.forename: T
authors.initials: T
authors.lastname: Okamura
authors.forename: E M
authors.initials: EM
authors.lastname: Garland
authors.forename: T
authors.initials: T
authors.lastname: Masui
authors.forename: T
authors.initials: T
authors.lastname: Sakata
authors.forename: M
authors.initials: M
authors.lastname: St John
authors.forename: S M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000139:chemically induced; D004326:Drinking / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005200:FANFT; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D010212:Papilloma / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D012439:Saccharin / Q000633:toxicity*; D012964:Sodium / Q000009:adverse effects; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
chemical_list: D005200:FANFT; D012964:Sodium; D012439:Saccharin