Ammonium-chloride-induced prostatic hypertrophy in vitro: urinary ammonia as a potential risk factor for benign prostatic hyperplasia

To test the possibility that urinary ammonia could be a risk factor for ben ign prostatic hyperplasia (BPH), we explored the cellular effects of ammoni um chloride (NH4Cl) on prostatic cancer cells used as an experimental model . Following treatment of human prostatic cancer DU-145 cells with the varyi ng concentrations of NH4Cl for 3 days, cell growth was inhibited by approxi mately 50% at 5 mM NH4Cl and almost completely inhibited at 10 mM NH4Cl. Ho wever, the individual cell size in these treated cells became approximately 2-fold larger and cellular protein content was also up to 2.5-fold greater -than in untreated cells. This protein increase appeared to result from the reduced protein degradation, verified by metabolic labeling with [C-14]val ine. Western blot analysis further suggested that such reduced protein turn over could in part be due to the inactivation of a lysosomal acid protease, cathepsin D. Taken together, these studies demonstrate NH4Cl-induced hyper trophy in prostatic cancer cells, as evidenced by the growth inhibition, ce ll enlargement, and cellular protein increase. Therefore, ammonia, is not a n inert metabolic product; instead, its chronic effects on the prostate may ultimately lead to significant cellular and biochemical alterations of the prostate such as BPH.