A proposed role for silicates and protein in the proliferative effects of saccharin on the male rat urothelium.
High doses of sodium saccharin, a non-genotoxic chemical, lead to the formation of silicate-containing precipitate and microcrystals in urine of male rats. Differences in urinary protein, pH, sodium and other factors affect silicate-containing precipitate and microcrystal formation as well as the bladder effects of sodium saccharin. Total urinary silicon concentration (mostly soluble) in sodium saccharin-fed rats is similar to or lower than the concentration in control rats. Binding of saccharin to male rat urinary proteins was demonstrated by equilibrium-gel filtration. We propose that by binding to urinary proteins under appropriate conditions, saccharin produces a nidus for the formation of silicate-containing precipitate and crystals. These appear to be cytotoxic to the superficial bladder epithelium, with cell death resulting in regenerative hyperplasia. Factors that influence the formation of these silicate-containing materials might provide a rationale for sex, species, dose and dietary differences in response to sodium saccharin.
Cohen
S M
SM
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135.
Cano
M
M
Earl
R A
RA
Carson
S D
SD
Garland
E M
EM
D000818:Animals; D002273:Carcinogens; D002850:Chromatography, Gel; D003460:Crystallization; D004848:Epithelium / Q000187:drug effects; D008297:Male; D011507:Proteinuria / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D012439:Saccharin / Q000633:toxicity*; D001743:Urinary Bladder / Q000187:drug effects*; D014961:X-Ray Diffraction
D002273:Carcinogens; D012439:Saccharin