title: Nitrosamine activation and detoxication through free radicals and their derived cations.
abstract: The enzymatic activation of simple dialkylnitrosamines is widely perceived to involve cytochrome P450-mediated alpha-hydroxylation to generate an unstable alpha-hydroxynitrosamine. This process can also result in the denitrosation of the nitrosamine, presumably through a common intermediate. We present evidence that the critical intermediate is the alkynitrosaminomethyl free radical, which we generated by thermal decomposition of a nitrosamino acid perester. The radical rapidly loses NO to generate an N-alkylmethyleneimine. The radical is also produced during the Ce(IV) oxidation of beta-hydroxynitrosamines after fragmentation, where it not only loses NO but is oxidized further to a cation which reacts with water to form an alpha-hydroxynitrosamine. These results provide models of the activation and detoxication pathways for beta-oxidized nitrosamines.
authors.affiliation: Department of Chemistry, University of Missouri, Columbia.
authors.forename: R N
authors.initials: RN
authors.lastname: Loeppky
authors.forename: Y E
authors.initials: YE
authors.lastname: Li
mesh_terms: D001711:Biotransformation; D005609:Free Radicals; D008658:Inactivation, Metabolic; D009569:Nitric Oxide / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism*
chemical_list: D005609:Free Radicals; D009602:Nitrosamines; D009569:Nitric Oxide