Photosensitized DNA damage induced by NADH: Site specificity and mechanism
Photosensitized DNA damage induced by NADH: Site specificity and mechanism
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DOI：
10.1080/10715760601145240
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Kawanishi, Shosuke
中科院分区：
文献类型：
--
作者：
Ito, Kimiko;Hiraku, Yusuke;Kawanishi, Shosuke
越来越多的证据表明UVA辐射的致癌性。我们证明，UVA照射的NADH诱导损伤的P-32标记的DNA片段从p53基因的存在下的Cu（II）。甲酰胺基嘧啶糖基化酶（FPG）敏感的病变形成在鸟嘌呤残基，而哌啶不稳定的病变经常发生在胸腺嘧啶残基。形成8-氧代-7，8-二氢-20-脱氧鸟苷（8-oxodG），UVA暴露在Cu（II）的存在下，增加依赖于NADH浓度。过氧化氢酶和铜（I）特异性螯合剂浴铜灵抑制DNA损伤，表明来自H2 O2和Cu（I）的反应物种的参与。UVA照射的核黄素诱导DNA裂解通过电子转移在50鸟嘌呤的5 '-GG-3'序列与Fpg和哌啶处理; Fpg诱导较少的切割在鸟嘌呤残基比哌啶。这些结果表明，NADH可能参与作为一种内源性光敏剂在UVA致癌通过H2 O2的产生，产生金属介导的诱变损伤，如8-oxodG。
Increasing evidence reveals the carcinogenicity of UVA radiation. We demonstrated that UVA-irradiated NADH induced damage to P-32-labeled DNA fragments obtained from the p53 gene in the presence of Cu( II). Formamidopyrimidine glycosylase ( Fpg)-sensitive lesions were formed at guanine residues, whereas piperidine-labile lesions occurred frequently at thymine residues. Formation of 8-oxo-7,8-dihydro-20-deoxyguanosine ( 8-oxodG), upon UVA exposure in the presence of Cu( II), increased depending on NADH concentration. Catalase and bathocuproine, a Cu( I)-specific chelator, inhibited the DNA damage, suggesting the involvement of reactive species derived from H2O2 and Cu( I). UVA-irradiated riboflavin induced DNA cleavage through electron transfer at 50 guanine of the 5'-GG-3' sequence with both Fpg and piperidine treatments; Fpg induced less cleavage at the guanine residues than piperidine. These results imply that NADH may participate as an endogenous photosensitizer in UVA carcinogenesis via H2O2 generation, producing metal-mediated mutagenic lesions such as 8-oxodG.