Cohen S M, Cano M, Earl R A, Carson S D, Garland E M
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135.
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.
高剂量的糖精钠（一种非遗传毒性化学物质）会导致雄性大鼠尿液中形成含硅酸盐的沉淀物和微晶。尿蛋白、pH值、钠及其他因素的差异会影响含硅酸盐沉淀物和微晶的形成以及糖精钠对膀胱的影响。喂食糖精钠的大鼠尿液中总硅浓度（大多为可溶性）与对照大鼠的浓度相似或更低。通过平衡凝胶过滤证明了糖精与雄性大鼠尿蛋白的结合。我们提出，在适当条件下，糖精通过与尿蛋白结合，产生一个形成含硅酸盐沉淀物和晶体的核心。这些似乎对膀胱浅表上皮细胞具有细胞毒性，细胞死亡导致再生性增生。影响这些含硅酸盐物质形成的因素可能为糖精钠反应中的性别、物种、剂量和饮食差异提供一个理论依据。
