A proposed role for silicates and protein in the proliferative effects of saccharin on the male rat urothelium

Carcinogenesis. 1991 Sep;12(9):1551-5. doi: 10.1093/carcin/12.9.1551.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinogens*
  • Chromatography, Gel
  • Crystallization
  • Epithelium / drug effects
  • Male
  • Proteinuria / chemically induced*
  • Rats
  • Rats, Inbred F344
  • Saccharin / toxicity*
  • Urinary Bladder / drug effects*
  • X-Ray Diffraction


  • Carcinogens
  • Saccharin