Guanine-specific DNA damage photosensitized by the dihydroxo(tetraphenylporphyrinato)antimony(V) complex.
Guanine-specific DNA damage photosensitized by the dihydroxo(tetraphenylporphyrinato)antimony(V) complex.
复制标题
DOI：
10.1016/j.jphotobiol.2005.08.008
复制
发表时间：
2006-01
期刊：
影响因子：
--
通讯作者：
Kazutaka Hirakawa;S. Kawanishi;Jin Matsumoto;T. Shiragami;M. Yasuda
中科院分区：
文献类型：
--
作者：
Kazutaka Hirakawa;S. Kawanishi;Jin Matsumoto;T. Shiragami;M. Yasuda
二羟基（四苯基卟啉）锑（V）络合物（SbTPP）在可见光照射下表现出杀菌活性。这种光毒性效应可能是由生物分子的光损伤引起的，但其机制尚不清楚。在本研究中，为了阐明 SbTPP 的光毒性机制，使用 [32P]-5' 末端标记的 DNA 片段检查了 SbTPP 光敏化的 DNA 损伤。 SbTPP 对单链 DNA 而非双链 DNA 造成明显严重的光损伤。在大肠杆菌甲酰胺嘧啶-DNA 糖基化酶或哌啶处理后，光照射的 SbTPP 经常导致单链 DNA 鸟嘌呤残基处的 DNA 裂解。 HPLC测定证实形成了2'-脱氧鸟苷的氧化产物8-oxo-7,8-二氢-2'-脱氧鸟苷（8-oxodG），并表明单链DNA中8-oxodG的含量高于双链DNA。活性氧清除剂对 DNA 损伤的影响表明单线态氧的参与。这些结果表明，SbTPP 的光毒性主要是通过单线态氧形成的机制造成的。另一方面，SbTPP 特异性地在双链 DNA 中 5'-GG、5'-GGG 和 5'-GGGG 的下划线 G 处诱导 DNA 损伤。 DNA 损伤的序列特异性与 I 型光敏剂诱导的损伤非常相似，表明光诱导的电子转移轻微参与了 SbTPP 的光毒性。总之，SbTPP 通过单线态氧形成和光诱导电子转移诱导 DNA 光损伤。类似的机制可以损害其他生物大分子，例如蛋白质和磷脂膜。通过这些机制对生物大分子的损伤可能参与了 SbTPP 的光毒性。
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 [32P]-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.