Oxidation and glycolytic cleavage of etheno and propano DNA base adducts.

Non-invasive strategies for the analysis of endogenous DNA damage are of interest for the purpose of monitoring genomic exposure to biologically produced chemicals. We have focused our research on the biological processing of DNA adducts and how this may impact the observed products in biological matrixes. Preliminary research has revealed that pyrimidopurinone DNA adducts are subject to enzymatic oxidation in vitro and in vivo and that base adducts are better substrates for oxidation than the corresponding 2′-deoxynucleosides. We tested the possibility that structurally similar exocyclic base adducts may be good candidates for enzymatic oxidation in vitro. We investigated the in vitro oxidation of several endogenously occurring etheno adducts [1,N2-e-guanine (1,N2-e-Gua), N2,3-e-Gua, heptanone-1,N2-e-Gua, 1,N6-e-adenine (1,N6-e-Ade), and 3,N4-e-cytosine (3,N4-e-Cyt)] and their corresponding 2′-deoxynucleosides. Both 1,N2-e-Gua and heptanone-1,N2-e-Gua were substrates for enzymatic oxidation in rat liver ...