Abstract

Membrane potentials of the urinary bladder epithelium in F344 male rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) or sodium saccharin were measured. In experiment 1, membrane potentials were measured sequentially in the early stage of their change on treatment with 0.05% BBN in the drinking water or with basal diet containing 5% sodium saccharin. Membrane potentials were measured with microelectrodes in weeks 1, 2, 4 and 8 of the experiment. The potential of the group treated with BBN was significantly higher than that of the controls from as early as week 1 until the end of the experiment. In experiment 2, the dose-dependence of the effects of BBN and sodium saccharin on the membrane potential was examined. F344 male rats were treated with 0.05, 0.01, 0.005 or 0.001% BBN in the drinking water, or 5, 1, 0.2 or 0.04% sodium saccharin in basal diet. Clear dose-dependence was observed in the effect of BBN on the potential, but of the doses of sodium saccharin used, only 5% saccharin caused a significantly higher potential than in the control group. These findings suggested that in the early stage of urinary bladder carcinogenesis induced by BBN, the Na+ channel located in the apical membrane may be inactivated.

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