COVALENT BINDING TO DNA IN-VITRO OF 2',3'-OXIDES DERIVED FROM ALLYLBENZENE ANALOGS

Epoxidation at the allylic side chain is a major metabolic pathway for allylbenzene and its naturally occurring analogs safrole, estragole, and eugenol, We demonstrate herein that the epoxide metabolites of all ylbenzene, estragole, and safrole can; form covalent adducts with DNA in vitro, binding primarily to guanine, but also to the other three DN A bases. Epoxide hydrolases can prevent the binding of allylbenzene 2' ,3'-oxide to DNA in vitro. Four distinct adducts were detected by anal ytical TLC after the reaction of 2'-deoxyguanosine with allylbenzene 2 ',3'-oxide. One unstable adduct was formed rapidly, but gradually disa ppeared, whereas the other three adducts were formed more slowly but p ersisted, The major persistent adduct, which was isolated by preparati ve chromatography, was examined by MS and NMR. The structure of this a dduct is 3'-N-1-deoxyguanosyl-(2'-hydroxypropylbenzene). In addition, a generally applicable paradigm for the identification of deoxyguanosi ne or guanosine adducts by C-13 and H-1 NMR spectroscopy is presented.