Formation of 1,N2- and N2,3-ethenoguanine from 2-halooxiranes: isotopic labeling studies and isolation of a hemiaminal derivative of N2-(2-oxoethyl)guanine.

Vinyl halides are oxidized to 2-halooxiranes, which rapidly rearrange to 2-haloacetaldehydes. Both of these species can react with DNA to generate a variety of adducts, including the potentially mutagenic etheno (e) products. Evidence was provided through kinetic studies that the e-Gua adducts are formed primarily from 2-haloxiranes; consistent with this view, epoxide hydrolase inhibited the formation of N 2 ,3-e-Gua from vinyl chloride but alcohol dehydrogenase did not. Assignments of the NMR shifts of the etheno protons of 1,N 2 - and N 2 ,3-e-Gua were made with the use of 15 N labeling and nuclear Overhauser effects, in revision of the literature