Sequence-specific DNA damage induced by ultraviolet A-irradiated folic acid via its photolysis product
Sequence-specific DNA damage induced by ultraviolet A-irradiated folic acid via its photolysis product
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DOI：
10.1016/s0003-9861(02)00722-1
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发表时间：
2003-02-15
影响因子：
3.9
通讯作者：
Kawanishi, S
中科院分区：
文献类型：
--
作者：
Hirakawa, K;Suzuki, H;Kawanishi, S
光敏剂介导的DNA损伤参与日光致癌。荧光测量和高效液相色谱分析表明，光照射细胞中的光敏剂之一叶酸，生成蝶呤-6-羧酸（PCA）。使用从人基因获得的P-32标记的DNA片段的实验表明，紫外线A照射的叶酸或PCA引起DNA切割特异性地在大肠杆菌formamidopyrimidine-DNA糖基化酶或哌啶处理后的双链DNA中的连续G残基。在双链DNA中通过这种DNA光反应形成的8-氧代-7，8-二氢-2’-脱氧鸟苷的量超过了单链DNA中的量。动力学研究表明，DNA损伤主要是由叶酸产生的光激发PCA引起的，而不是叶酸本身。总之，光照射叶酸产生PCA，诱导DNA光氧化，特别是在连续的G残基通过电子转移。过量摄入叶酸补充剂可能会增加太阳紫外线引起的皮肤癌的风险。(C)2002 Elsevier Science（美国）。All rights reserved.
DNA damage mediated by photosensitizers participates in solar carcinogenesis. Fluorescence measurement and high-performance liquid chromatography analysis demonstrated that photoirradiated folic acid, one of the photosensitizers in cells, generates pterine-6-carboxylic acid (PCA). Experiments using P-32-labeled DNA fragments obtained from a human gene showed that ultraviolet A-irradiated folic acid or PCA caused DNA cleavage specifically at consecutive G residues in double-stranded DNA after Escherichia coli formamidopyrimidine-DNA glycosylase or piperidine treatment. The amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine formed through this DNA photoreaction in double-stranded DNA exceeded that in single-stranded DNA. Kinetic studies suggested that DNA damage is caused mainly by photoexcited PCA generated from folic acid rather than by folic acid itself. In conclusion, photoirradiated folic acid generates PCA, which induces DNA photooxidation specifically at consecutive G residues through electron transfer. Excess intake of folic acid supplements may increase a risk of skin cancer by solar ultraviolet light. (C) 2002 Elsevier Science (USA). All rights reserved.