Research Program Area: Health & Exposure
Topic Areas: Health Effects of Air Pollution
We have investigated the previously unknown metabolic fate of nitrate (NO3) and nitrite (NO2) after introduction into the respiratory tract because they exist in the ambient California urban aerosol or can be derived from known nitrogenous air pollutants such as nitrogen dioxide (NO2), nitric acid (HNO3), or nitrous acid (HNO2). This study deals exclusively with chemically neutral sources of NO3 and N02. Nitrate and nitrite distribution and metabolic chemistry measurements in blood fractions and pertinent organs of both mice or rabbits ware made possible by our development of new radiochemical methods. Radioactive nitrogen-13 (t 1/2 =l0 min) has been used to synthesize 13 NO3 - solutions with radioactivity concentrations of 230 mCi/mL and 13 NO2- solution: with radioactivity concentrations of 150 mCi/ml (Section 5). These concentrations are 10-100 million times our minimum detectable quantity and permit longer, more complex biochemical tracer experiments than previously possible. The radioactive label allowed us to account for 100% of the administered nitrogen throughout the period required for metabolism of the original species. We have found that 13 NO2 - and 13 NO3 - are cleared rapidly from the lungs in the presence and absence of added carrier. Both anions penetrate the red cell membrane and NO2 is converted to NO3 which diffuses out. The N-13 label from both anions was loosely bound to plasma and cellular proteins but did not form a covalent bond (Section 6, 7). Nitrate does not undergo detectable reactions in blood. Nitrite is oxidized to nitrate in blood cells and not in plasma. In mice, over 70% was oxidized within ten mininutes, and in rabbits, only 46% was oxidized within ten minutes. Comparable in vivo and in vitro oxidation rates for mice and rabbits suggest that in vivo oxidation of nitrite to nitrate can be estimated for humans from in vitro blood studies and provide a basis for interspecies extrapolation of NO2 gas toxicity studies. A preliminary model of nitrate and nitrite metabolism after introduction into the respiratory tract is proposed (Section 7). We previously observed an unidentified non-anionic compound or mixture of labeled compounds in blood and now have found it to be derived from metabolic reactions in the gastrointestinal tract where the possibility of forming carcinogenic nitrosamines exists. The compounds formed in the intestines by bacteria were found to be naturally occurring ammonia, glutamate, glutamine and small amounts of urea and neutral amino acids. A selective search for simple nitrosamines did not reveal their presence under our experimental conditions.
For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753
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