Iqbal et al. in 1980 reported that N-nitrosomorpholine (NMOR) was produced in mice gavaged with morpholine and exposed to atmospheric nitrogen dioxide (NO2). We demonstrated that this NMOR formation occurs by an in vitro reaction in the mouse homogenate between morpholine and a nitrosating agent (NSA), produced in vivo from NO2. We wish to study this NSA in depth because it could produce carcinogenic nitrosamines and nitrosamides in vivo. The following are our specific aims. (1) Chemical identification of the NSA produced in vivo by NO2. (2) Search for amines and amides nitrosated in vivo by the NSA. (3) Search for nitramines as products of the in vivo reaction between NO2 and amines. (4) Studies on the amount of NSA produced with varied doses of NO2. (5) Distribution of the NSA in different tissues, at varying NO2 concentrations and exposure periods. (6) Appearance and disappearance rates of NSA in the body after NO2 exposure. (7) Possible NSA formation from nitrite. (8) Effect of inhibitors on NSA formation. (9) Metabolic fate of the NSA. (10) Studies on model nitrostates (Alpha-nitronitrite esters), since nitrosates are most likely to be the in vivo NSA, produced from NO2 and unsaturated lipids.
