potassium-permanganate and 8-hydroxyguanine

Recently we found that KMnO4 oxidation of DNA oligomers containing a 7,8-dihydro-8-oxoguanine (8-oxo-G) residue induces damage to the neighboring base residues; other modified bases, 7,8-dihydro-8-oxoadenine (8-oxo-A) and 5-hydroxyuracil (5-oh-U), show similar behavior in DNA. The present study indicated that the ability to induce damage, which could also occur by the oxidation of a 5-oh-C residue, was low as in the case of 5-oh-U. On the other hand, in order to examine the pathways and the intermediates for the oxidative degradation of 8-oxo-A, we have carried out the KMnO4 oxidation using an 8-oxo-2'-deoxyadenosine derivative as a model and have determined the structures of the three major products.

Topics: Adenine; Base Sequence; DNA; DNA Damage; Guanine; Oligodeoxyribonucleotides; Oxidation-Reduction; Potassium Permanganate; Uracil

New types of DNA substrates containing an 8-oxoguanine residue (8-oxo-G) were prepared in order to examine the mechanisms for the neighboring base damage initiated by KMnO4 oxidation of the 8-oxo-G. The results obtained from the reactions suggested that the damage at remote sites in the single strands can be explained by an electronic interaction (redox reaction) between an oxidized 8-oxo-G species and the base (to be damaged), which are close each other in a loop structure. For the inefficient damage observed in duplex substrates, electron transfer through stacked bases might be involved.

Topics: Base Sequence; DNA; DNA Damage; Guanine; Hydrolysis; Nucleic Acid Conformation; Oligodeoxyribonucleotides; Oxidation-Reduction; Potassium Permanganate

Single-stranded M13mp2 DNA was oxidized with 0.8 mM KMnO4 at pH 8.6 and 4 degrees C for 5 min. These are conditions used previously by Akman et al. (Arch. Biochem. Biophys., 1990, 282, 202) for the oxidation of a denatured DNA and the authors reported that 8-hydroxyguanine was formed in the DNA with this treatment. We decomposed the oxidized DNA with heating in formic acid and the resulting bases were analyzed by HPLC. No significant 8-hydroxyguanine formation was detected in this sample. We also investigated the consumption of KMnO4 by nucleosides. Under conditions in which thymidine consumed KMnO4 rapidly, very little consumption was found with deoxyguanosine (less than 1/100, in rate, compared to that by thymidine). These results show that the permanganate oxidation of DNA does not result in the formation of 8-hydroxyguanine.

Topics: Deoxycytidine; Deoxyguanosine; DNA Damage; DNA, Single-Stranded; DNA, Viral; Guanine; Hydrogen-Ion Concentration; Kinetics; Oxidation-Reduction; Potassium Permanganate; Thymidine