Carcinogenic N‐nitrosamine formation: A requirement for nitric oxide

Abstract

This paper provides evidence that nitric oxide is required for the aqueous nitrosation of amines by nitrogen dioxide and that the rate of reaction is first‐order for both nitrogen oxide species. The formation of nitrosamines in the organic phase is also first‐order with respect to nitric oxide concentration, but unlike the aqueous phase reaction, extrapolation to zero NO concentration suggests that some nitrosation from N₂O₄ may occur. We attribute previous reports of nitrosation of amines by nitrogen dioxide in aqueous solution to the presence of nitric oxide as a contaminant found in tanks of compressed nitrogen dioxide. We also report that phenols do not enhance nitrosation by NO2 in the presence of NO. Although much previous research in vitro and in vivo has focused on the role of nitrogen dioxide in amine nitrosation, the results reported here suggest that nitric oxide levels may be of greater significance with regard to the formation of nitrosamines.