Chemopreventive action of xanthone derivatives on photosensitized DNA damage
Chemopreventive action of xanthone derivatives on photosensitized DNA damage
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DOI：
10.1562/2004-07-29-ra-252.1
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Kawanishi, S
中科院分区：
文献类型：
--
作者：
Hirakawa, K;Yoshida, M;Kawanishi, S
光敏DNA损伤参与太阳紫外线致癌、光遗传毒性和光毒性。化学预防光敏DNA损伤是上述光毒性效应的重要方法之一。本研究利用[P-32]-5 ′-末端标记的人类肿瘤相关基因DNA片段，证明了山酮（XAN）衍生物（bellidifolin [BEL]，gentiacaulein [GEN]，norswertianin [NOR]和swerchirin [SWE]）对核黄素光敏化DNA损伤的化学预防作用。GEN和NOR有效地抑制了光激发核黄素在连续G残基上形成哌啶不稳定产物，而BEL和SWE对DNA损伤没有明显的抑制作用。这四种XAN衍生物通过光激发的核黄素减少G的氧化产物8-氧代-7，8-二氢-2 '-脱氧鸟苷（8-oxodGuo）的形成。这些XAN衍生物对8-oxodGuo形成的预防作用按以下顺序增加：GEN > NOR >> BEL > SWE。荧光光谱研究和从头算分子轨道计算表明，DNA光损伤的预防是因为XAN衍生物通过电子转移猝灭核黄素的三重激发态。这种化学预防既不是基于抗氧化作用，也不是基于物理防晒作用;相反，它是基于光敏剂的猝灭。总之，XAN衍生物，特别是GEN，可以作为一种新的化学预防剂的激发光敏剂的猝灭机制。
Photosensitized DNA damage participates in solar-UV carcinogenesis, photogenotoxicity and phototoxicity. A chemo-prevention of photosensitized DNA damage is one of the most important methods for the above phototoxic effects. In this study, the chemopreventive action of xanthone (XAN) derivatives (bellidifolin [BEL], gentiacaulein [GEN], norswer-tianin [NOR] and swerchirin [SWE]) on DNA damage photosensitized by riboflavin was demonstrated using [P-32]-5'-end-labeled DNA fragments obtained from genes relevant to human cancer. GEN and NOR effectively inhibited the formation of piperidine-labile products at consecutive G residues by photoexcited riboflavin, whereas BEL and SWE did not show significant inhibition of DNA damage. The four XAN derivatives decrease the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidative product of G, by photoexcited riboflavin. The preventive action for the 8-oxodGuo formation of these XAN derivatives increased in the following order: GEN > NOR >> BEL > SWE. A fluorescence spectroscopic study and ab initio molecular orbital calculations suggested that the prevention of DNA photodamage is because of the quenching of the triplet excited state of riboflavin by XAN derivatives through electron transfer. This chemoprevention is based on neither antioxidation nor a physical sunscreen effect; rather, it is based on the quenching of a photosensitizer. In conclusion, XAN derivatives, especially GEN, may act as novel chemopreventive agents by the quenching mechanism of an excited photosensitizer.