P24: Effects of iodide on nitrite reduction by ascorbate and implications on nitrosoamine formation

Background Under acidic conditions of the stomach with gastric juice pH ranging from 1.7 to 2.6, nitrite is reduced to nitric oxide. When a diet rich in nitrate is consumed, it is partially reduced to nitrite in the mouth by oral bacteria followed by ingestion and partial reduction of nitrite to nitric oxide (NO) in the stomach. When the dietary nitrate is consumed along with protein, secondary amines from protein react with nitrite via the formation of reactive nitrogen species to form nitrosamines, which are carcinogenic. Ascorbic acid, also obtained from diet, can react with nitrite to form NO in the acidic gastric juice, which does not react with amines. Ascorbate has a protective effect on the formation of carcinogenic compounds like nitrosamines by reducing nitrite faster and out competing nitrosamine formation by reactive oxygen species and amines. Iodide can also reduce nitrite to NO in acidic pH, which is the basis of a nitrite assay used in nitric oxide analyzers. Although it has been suggested that dietary iodide would lead to increased nitrosamine formation the enhanced formation of NO from nitrite due to iodide suggests iodide would be protective against nitrosamine formation. Thus, the combined effect of ascorbate and sodium iodide in the presence of nitrite and amines under acidic conditions on nitrosamine formation was studied. Methods In this study the effect of ascorbic acid and sodium nitrite on nitrite reduction and nitrosamine formation was determined in vitro. Nitrite reduction to NO was determined under anaerobic conditions by ozone chemiluminescence by the Nitric Oxide Analyzer (NOA 280i, Sievers, GE Analytical Instruments, Boulder, CO). Nitrosamine concentrations were measured using absorption spectroscopy according to a modification of method by Mirvish et al., Science 175 (1972) 65–68. Results Both Iodide and ascorbic acid are effective in reducing nitrite to NO at the pH range that includes the pH of stomach. There is a synergistic effect of ascorbic acid and iodide on the rates of nitrite reduction to NO. Very low levels of nitrite are reduced to NO by either ascorbic acid or iodide alone. Nitrosomorpholine formation is reduced by iodide and ascorbate combined compared to ascorbic acid alone at pH 2. Conclusions The results indicate that, due to the increased rate of nitrite reduction byascorbic acid in the presence of iodide, nitrosation of morpholine to nitrosomorpholine can be reduced. Given that both nitrate and iodide are taken up by salivary glands and concentrated in the oral cavity, their combined effects on nitrosamine formation could have substantial impact. Disclosure This work was supported by NIH Grant HL058091.