Base Oxidation at 5′ Site of GG Sequence in Double-stranded DNA Induced by UVA in the Presence of Xanthone Analogues: Relationship Between the DNA-damaging Abilities of Photosensitizers and Their HOMO Energies ¶

Abstract

UVA contributes to skin cancer by solar UV light. Photosensitizers are believed to play an important role in UVA carcinogenesis. We investigated the mechanism of DNA damage induced by photoexcited xanthone (XAN) analogues (XAN, thioxanthone [TXAN] and acridone [ACR]), exogenous photosensitizers, and the relationship between the DNA‐damaging abilities and their highest occupied molecular orbital (HOMO) energies. DNA damage by these photosensitizers was examined using 32P‐labeled DNA fragments obtained from the p53 tumor suppressor gene. Photoexcited XAN caused DNA cleavage specifically at 5′‐G of the GG sequence in the double‐stranded DNA only when the DNA fragments were treated with piperidine, suggesting that DNA cleavage is due to base modification with little or no strand breakage. With denatured single‐stranded DNA, the extent of XAN‐sensitized photodamage was decreased. An oxidative product of G, 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxo‐dGuo), was formed by photoexcited XAN, and the 8‐oxo‐dGuo formation was decreased in single‐stranded DNA. TXAN and ACR induced DNA photodamage as did XAN, although the order of DNA‐damaging ability was XAN > TXAN > ACR. These findings suggest that photoexcited XAN analogues induce nucleobase oxidation at 5′‐G of GG sequence in double‐stranded DNA through electron transfer. The HOMO energies of these photosensitizers, estimated from ab initio molecular orbital (MO) calculation, decreased in the following order: XAN > TXAN > ACR. Extents of DNA damage increased exponentially with the HOMO energies of XAN analogues. This study suggests that DNA‐damaging abilities of photosensitizers can be estimated from their HOMO energies.

Light-induced transformations of aza-aromatic pollutants adsorbed on models of atmospheric particulate matter: Acridine and 9(10-H) acridone

“…Its formation can be considered as a potential environment hazard, because photoexcited acridine is known to induce DNA damage (Hirakawa et al, 2003). Photoinduced tautomerism of acridone on the surfaces resulted in the formation of 9-hydroxyacridine, its principal product.…”

Effect of Quadruplex Conformation on Radiation-Induced Formation of 8-Hydroxyguanine and Unaltered Base Release in Polyguanylic Acid

“…Previous work showed that the radiation-induced yields of 8-OHG in double-stranded DNA were 20- and twofold higher in DNA compared with those in deoxyguanosine in the presence and absence of oxygen, respectively (34). On the other hand, the formation of 8-OHG after UV irradiation in the presence of various photosensitizers was significantly lower for the single-stranded DNA conformation compared with the double-stranded conformation (35). Such disagreements between existing data can be caused by differences in experimental conditions (e.g., ionizing or UV radiation) that can lead to variations in the relative yields of the stable products from guanine radiolysis.…”

Superoxide Dismutase Enhanced the Formation of Hydroxyl Radicals in a Reaction Mixture Containing Xanthone under UVA Irradiation

“…Of the photosensitizers, xanthone and its derivatives have been extensively examined for UVA-induced DNA damage. 11,12) It has been found that xanthone mediates the photosensitized decomposition of fatty ester hydroperoxides to produce oxyl radicals 13) and hydroxyl radicals, 14,15) but to our knowledge, no study focusing on molecular oxygen-derived radicals has been performed. In this study, we detected hydroxyl radical and clarified the reaction mechanism in a reaction mixture of xanthone under UVA irradiation.…”