Photosensitized DNA damage and its protection via a novel mechanism.
UVA, which accounts for approximately 95% of solar UV radiation, can cause mutations and skin cancer. Based mainly on the results of our study, this paper summarizes the mechanisms of UVA-induced DNA damage in the presence of various photosensitizers, and also proposes a new mechanism for its chemoprevention. UVA radiation induces DNA damage at the 5'-G of 5'-GG-3' sequence in double-stranded DNA through Type I mechanism, which involves electron transfer from guanine to activated photosensitizers. Endogenous sensitizers such as riboflavin and pterin derivatives and an exogenous sensitizer nalidixic acid mediate DNA photodamage via this mechanism. The major Type II mechanism involves the generation of singlet oxygen from photoactivated sensitizers, including hematoporphyrin and a fluoroquinolone antibacterial lomefloxacin, resulting in damage to guanines without preference for consecutive guanines. UVA also produces superoxide anion radical by an electron transfer from photoexcited sensitizers to oxygen (minor Type II mechanism), and DNA damage is induced by reactive species generated through the interaction of hydrogen peroxide with metal ions. The involvement of these mechanisms in UVA carcinogenesis is discussed. In addition, we found that xanthone derivatives inhibited DNA damage caused by photoexcited riboflavin via the quenching of its excited triplet state. It is thus considered that naturally occurring quenchers including xanthone derivatives may act as novel chemopreventive agents against photocarcinogenesis.
Hiraku
Yusuke
Y
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Ito
Kimiko
K
Hirakawa
Kazutaka
K
Kawanishi
Shosuke
S
D004249:DNA Damage / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D004579:Electron Transport; D005609:Free Radicals / Q000378:metabolism; D006147:Guanine / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism; D017319:Photosensitizing Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000528:radiation effects; D012256:Riboflavin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000528:radiation effects; D026082:Singlet Oxygen / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
D005609:Free Radicals; D008670:Metals; D017319:Photosensitizing Agents; D044004:Xanthones; D013481:Superoxides; D026082:Singlet Oxygen; D006147:Guanine; C009689:xanthone; D006861:Hydrogen Peroxide; D043382:DNA-Formamidopyrimidine Glycosylase; D010100:Oxygen; D012256:Riboflavin