Abstract
It is well known that reactive oxygen species, UV and radiation can induce sequence-specific DNA damage. We have investigated sequence specificity of oxidative stress-mediated DNA damage by using 32P-labeled DNA fragments (human c-Ha-ras-1, p16, p53 genes and telomeric oligonucleotide). Free hydroxyl radical and peroxynitrite cause DNA damage with no marked site specificity. Singlet oxygen (1O2)-mediated DNA damage is caused at every guanine. Furthermore, sulfate radicals, nitrogen-centered radicals and oxygen-centered radicals show different sequence specificity. UVA radiation also causes DNA damage at the 5'-G in GG through electron transfer in the presence of certain photosensitizers. This guanine is easily oxidized because a large part of the highest occupied molecular orbital is distributed on this site. On the basis of these findings, the sequence specificity of DNA damage is presumably determined by (a) redox potential of reactive species; (b) ionization potential of DNA bases; (c) site-specific binding of metal ion to DNA. Here we discuss the mechanisms of sequence-specific DNA damage in relation to carcinogenesis and aging. [J Radiat Res 44:381 (2003)]
