Reactive Metabolites from N-Nitrosamines

N-Nitrosodialkylamines are metabolically activated by hydroxylation at the carbon atom alpha to the N-nitroso group. Spontaneous cleavage of the C-N bond in the α-hydroxynitrosamine leads to production of an alkydiazohydroxide that decomposes to an alkydiazonium ion. In principle, the diazonium ion can lose nitrogen to form a carbonium ion, although we have presented evidence that carbonium ions are not involved in DNA alkylation (Park et al., 1980). It is not known which of the activated species first interacts with the DNA. The α-hydroxynitrosamine has a half life of the order of seconds at physiological pH (Mochizuki et al., 1980), and may be the transport form of the activated carcinogen (Gold and Linda, 1979) which diffuses from its site of synthesis into the nucleus. The α-hydroxynitrosamine may also be the species which first interacts with the DNA.