The in vitro effects of saccharin were evaluated in a transformed rat-bladder epithelial cell line. AY-27 cells were seeded in a 35-mm tissue culture well and incubated for 24 hr with saccharin or other test compounds dissolved in the media. The cytotoxic effects of saccharin were dependent on the salt form tested. Although dose-related decreases in cell viability and attachment were observed following exposure to sodium or potassium saccharin at concentrations of ≥50 mM, calcium saccharin decreased only cell viability. Sodium chloride, sodium ascorbate and sodium citrate decreased cell viability and attachment in a dose-related fashion, whereas neither potassium chloride nor calcium chloride had any effect. The finding that all of the tested sodium compounds were cytotoxic suggests that the sodium ion plays a role in the cytotoxicity of sodium saccharin. However, the maximum effect and potency of the sodium compounds differed, indicating that the anion moiety also contributes to the cytotoxic effect. Although effects were observed only at millimolar concentrations of the sodium salts, these concentrations corresponded to those in the urine that produced a urothelial proliferative response in rats fed these compounds in earlier studies.
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