NEIGHBORING BASE DAMAGE-INDUCED BY PERMANGANATE OXIDATION OF 8-OXOGUANINE IN DNA

We found that single-stranded DNA oligomers containing a 7,8-dihydro-8 -oxoguanine (8-oxo-G) residue have high reactivity toward KMnO4; the o xidation of 8-oxo-G induces damage to the neighboring nucleotide resid ues. This paper describes the novel reaction in detail, including expe riments that demonstrate the mechanism involved in the induction of DN A damage. The results using DNAs of various base compositions indicate d that damaged G, T and C (but not A) sites caused strand scissions af ter hot piperidine treatment and that the damage around the 8-oxo-G oc curred at G sites in both single and double strands with high frequenc y, The latter substrates were less sensitive to damage. Further, kinet ic studies of the KMnO4 reaction of single-stranded oligomers suggeste d that the reactivity of the DNA bases at the site 5'-adjacent to the 8-oxo-G was in the order G > A > T, C, This preference correlates with the electron donating abilities of the bases. In addition, we found t hat the DNA damage at the G site, which was connected with the 8-oxo-G by a long abasic chain, was inhibited in the above order by the addit ion of dG, dA or dC. On the other hand, the damage reactions proceeded even after the addition of scavengers for active oxygen species. This study suggests the involvement of a redox process in the unique DNA d amage initiated by the oxidation of the 8-oxo-G.