Guanine-specific DNA oxidation photosensitized by the tetraphenylporphyrin phosphorus(V) complex via singlet oxygen generation and electron transfer
Guanine-specific DNA oxidation photosensitized by the tetraphenylporphyrin phosphorus(V) complex via singlet oxygen generation and electron transfer
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DOI：
10.1016/j.jphotobiol.2007.04.001
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发表时间：
2007-06-26
影响因子：
5.4
通讯作者：
Segawa, Hiroshi
中科院分区：
文献类型：
--
作者：
Hirakawa, Kazutaka;Kawanishi, Shosuke;Segawa, Hiroshi
研究了一种阳离子水溶性卟啉二羟P（V）四苯基卟啉（P（V）TPP）对DNA的光敏损伤作用。近红外发射测量的研究证实了P（V）TPP的光敏单线态氧（102）生成（在乙醇中的量子产率：0.28）。DNA对P（V）TPP的荧光猝灭表明了光激发态P（V）TPP与碱基之间的电子转移（ET）。这些结果表明，P（V）TPP具有通过102代和ET双重机制损伤DNA的能力。在有氧条件下，P（V）TPP光敏损伤是更严重的单链DNA相比，其双链对应。光激发的P（V）TPP破坏单链DNA中的每个鸟嘌呤残基。HPLC测定证实了2 '-脱氧鸟苷的氧化产物8-氧代-7，8-二氢-2'-脱氧鸟苷（8-oxodGuo）的形成，并表明单链DNA中8-oxodGuo的产率大于双链DNA中的产率。鸟嘌呤特异性的DNA损伤和单链DNA的增强表明O-1（2）代主要参与了P（V）TPP的DNA光损伤机制。吸收光谱测定表明P（V）TPP与DNA之间存在相互作用。由于102的寿命非常短，预期这种相互作用会增强O-1（2）介导的DNA损伤。另一方面，对于双链DNA，连续鸟嘌呤的光敏损伤要不那么明显。由于连续的鸟嘌呤作为空穴陷阱，这种DNA损伤模式表明光诱导ET的部分参与。但ET对DNA的损伤不是主要机制，可能是ET的逆转作用。总之，P（V）TPP主要通过10代诱导鸟嘌呤特异性光氧化。与DNA的相互作用和光激发卟啉的能级可能有利于O-1（2）介导的DNA损伤，而不是ET机制。(c)2007 Elsevier B. V.保留所有权利。
The photosensitized DNA damage caused by dihydroxoP(V)tetraphenylporphyrin (P(V)TPP), a cationic water-soluble porphyrin, was examined. The study of near-infrared emission measurements demonstrated the photosensitized singlet oxygen (102) generation by P(V)TPP (quantum yield: 0.28 in ethanol). The fluorescence quenching of P(V)TPP by DNA showed the electron transfer (ET) from nucleobases to photoexcited P(V)TPP. These results have shown that P(V)TPP has ability to damage DNA through dual mechanisms, 102 generation and ET. Under aerobic conditions, P(V)TPP photosensitized damage was more severe for single-stranded DNA compared to its double-stranded counterpart. Photoexcited P(V)TPP damaged every guanine residue in single-stranded DNA. HPLC measurements confirmed the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidized product of 2'-deoxyguanosine, and showed that the yield of 8-oxodGuo in single-stranded DNA is larger than that in double-stranded DNA. The guanine-specific DNA damage and the enhancement in single-stranded DNA suggest that the O-1(2) generation mainly contributes to the mechanism of DNA photodamage by P(V)TPP. Absorption spectrum measurements suggested the interaction between P(V)TPP and DNA. This interaction is expected to enhance the O-1(2)-mediated DNA damage since the lifetime Of 102 is very short. On the other hand, for double-stranded DNA, photosensitized damage at consecutive guanines was much less pronounced. Because the consecutive guanines act as a hole trap, this DNA-damaging pattern suggests the partial involvement of photoinduced ET. However, DNA damage by ET was not a main mechanism, possibly due to the reverse ET. In conclusion, P(V)TPP induces guanine specific photooxidation mainly via 10, generation. The interaction with DNA and the energy level of the photoexcited porphyrin may be advantageous for O-1(2)-mediated DNA damage rather than ET mechanism. (c) 2007 Elsevier B.V. All rights reserved.