The cancer-causing action of the alkaloid-derived nitrosamines (R1R2CH2NNO) found in unburned tobacco, tobacco smoke, and smokeless tobacco products has been investigated for many years. It has been established that in the human body cytochrome P450 activation of these nitrosamine species initially occurs by catalytic reaction of this enzyme to form an a-nitrosamine radical (R1R2C·HN-NO). This nitrosamine radical either combines with a hydroxyl radical (·OH) within the P450 catalytic site to form the DNA-alkylating a-hydroxynitrosamine (R1R2C(OH)HN-NO), or undergoes loss of nitric oxide. However, nitrosamine chemical activation can occur by a P450-independent pathway. This alternative pathway also requires the initial formation of the a-carbon radical, by reaction of a reactive oxygen species such as the hydroxyl radical, with subsequent reaction with oxygen to form the nitrosamine peroxyl radicals (R1R2C(O2)·HN-NO). To date, the formation of the carbon-centered a-nitrosamine radical has been well characterized. However, there has been very little study of the peroxyl radical formation chemistry, particularly for the tobacco-specific nitrosamines. In this work experiments were conducted to measure absolute peroxyl radical reaction rate constants for four tobacco-specific nitrosamines and four model compounds under physiological conditions. Measurement of these kinetic parameters will provide mechanistic insights into the importance of the alternative peroxyl radical formation pathway for nitrosamine carcinogenesis relative to the P450 pathway.

Radical-induced oxidation of tobacco-specific nitrosamines under physiological conditions

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.