Decay kinetics of nicotine/NNK-DNA adducts in vivo studied by accelerator mass spectrometry

The decay kinetics of nicotine-DNA adducts and NNK-DNA adducts in mice live r after single dosing was studied by accelerator mass spectrometry (AMS). T he decay is characterized by a two-stage process. The half-lives of nicotin e-DNA adducts are 1.3 d (P24 h) and 7.0 d (1-21 d), while for NNK-DNA adduc ts are 0.7 d (4-24 h) and 18.0 d (1-21 d). The relatively faster decay of n icotine-DNA adducts suggests that the genotoxicity of nicotine is weaker th an that of NNK. The in vitro study shows that the metabolization of nicotin e is necessary for the final formation of nicotine-DNA adducts, and nicotin e Delta1'(5') iminium ion is a probable metabolite species that binds to DN A molecule covalently. (C) 2000 Elsevier Science B.V. All rights reserved.