title: Guanine-specific DNA damage photosensitized by the dihydroxo(tetraphenylporphyrinato)antimony(V) complex.
abstract: The dihydroxo(tetraphenylporphyrinato)antimony(V) complex (SbTPP) demonstrates bactericidal activity under visible-light irradiation. This phototoxic effect could be caused by photodamage to biomolecules, but the mechanism has not been well understood. In this study, to clarify the mechanism of phototoxicity by SbTPP, DNA damage photosensitized by SbTPP was examined using [(32)P]-5'-end-labeled DNA fragments. SbTPP induced markedly severe photodamage to single-stranded rather than to double-stranded DNA. Photo-irradiated SbTPP frequently caused DNA cleavage at the guanine residue of single-stranded DNA after Escherichia coli formamidopyrimidine-DNA glycosylase or piperidine treatment. HPLC measurement confirmed the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidation product of 2'-deoxyguanosine, and showed that the content of 8-oxodG in single-stranded DNA is larger than that in double-stranded DNA. The effects of scavengers of reactive oxygen species on DNA damage suggested the involvement of singlet oxygen. These results have shown that the mechanism via singlet oxygen formation mainly contributes to the phototoxicity of SbTPP. On the other hand, SbTPP induced DNA damage specifically at the underlined G of 5'-GG, 5'-GGG, and 5'-GGGG in double-stranded DNA. The sequence-specificity of DNA damage is quite similar to that induced by the type I photosensitizers, suggesting that photo-induced electron transfer slightly participates in the phototoxicity of SbTPP. In conclusion, SbTPP induces DNA photodamage via singlet oxygen formation and photo-induced electron transfer. A similar mechanism can damage other biomacromolecules, such as protein and the phospholipid membrane. The damage to biomacromolecules via these mechanisms may participate in the phototoxicity of SbTPP.
authors.affiliation: Division of Applied Science and Basic Engineering, Faculty of Engineering, Shizuoka University, Johoku 3-5-1, Hamamatsu, Shizuoka 432-8561, Japan. tkhirak@ipc.shizuoka.ac.jp
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Hirakawa
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
authors.forename: Jin
authors.initials: J
authors.lastname: Matsumoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shiragami
authors.forename: Masahide
authors.initials: M
authors.lastname: Yasuda
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000378:metabolism*; D043382:DNA-Formamidopyrimidine Glycosylase / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism*; D008027:Light; D008563:Membrane Lipids / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; D008563:Membrane Lipids; D008665:Metalloporphyrins; D010743:Phospholipids; D017319:Photosensitizing Agents; D010880:Piperidines; D011506:Proteins; C509072:dihydroxo(tetraphenylporphyrinato)antimony(V); D026082:Singlet Oxygen; D006147:Guanine; C032727:piperidine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; D003849:Deoxyguanosine