Inhibition of Cancer Cell Replication by Inorganic Nitrite

Nitrite has been implicated in carcinogenesis, especially under acidic conditions such as in the stomach or in urine, where it forms nitrosating species that can react with secondary amines to form nitrosamines. Recent studies have shown that nitrite and acid form a variety of other nitrogen oxides in vivo including nitric oxide-a compound with documented antitumor activity. Here we tested the effects of nitrite on bladder tumor cells incubated in mildly acidified urine. Nitrite (50 mu M) inhibited thymidine incorporation in human T24 bladder cancer cells. This inhibition required slight acidification (pH 5.5-6), and no effect of nitrite could be observed at pH 7. Nitrite effects were further augmented in the presence of ascorbic acid, whereas ascorbic acid alone had no effect. The effects were paralleled by formation of nitric oxide gas. We here demonstrate an inhibitory effect of nitrite on cancer cell replication at concentrations and acidity commonly found in urine and gastric juice. The inhibitory effect is likely caused by nitric oxide and possibly other reactive nitrogen oxides formed from acidified nitrite.