Interstrand Crosslinking Involving Guanine: A New Major UVC Laser‐Induced Biphotonic Oxidatively Generated DNA Damage^†

Abstract

Several classes of oxidatively generated DNA damage including oxidized purine and pyrimidine bases, interstrand base crosslinks and DNA‐protein crosslinks have been previously shown to be generated in both isolated DNA and cellular DNA upon exposure to either 266‐nm laser irradiation or one‐electron oxidants. In this study, we provide evidence that biphotonic ionization of guanine bases by UVC laser irradiation of double‐stranded deoxyoligonucleotides in aerated aqueous solutions induces the formation of interstrand crosslinks (ICLs). This is supported by various experiments including sequencing gel analyses of formed photoproducts and effects of UVC laser intensity on their formation. This constitutes a novel example of the diversity of reactions of guanine radical cation that can be generated by various one‐electron oxidants including UVC laser biphotonic ionization, direct effect of ionization radiation and type I photosensitizers. However, the exact structure of the interstrand base adducts that is a challenging analytical issue remains to be further established. Examples of relevant biochemical/structural applications of biphotonic induction of ICLs in DNA samples by high‐intensity UVC laser pulses are provided.

DNA radiosensitization by terpyridine-platinum: damage induced by 5 and 10 eV transient anions

“…117 In addition to crosslinking, a diversity of reactions with guanine radicals exist, among which the most prominent is base release. 127,128 Considering the integrity of terpyridine after electron bombardment, suggested from the UV-Vis absorption spectrum (Fig. 1S †), the resulting G radicals could (1) follow the oxidation and/or reduction processes causing guanine-BDs and (2) abstract hydrogen from the backbones, leading to the cleavage of phosphodiester bonds, i.e., BD + SSB.…”