Intra- and extra-cellular DNA damage by harmine and 9-methyl-harmine
Intra- and extra-cellular DNA damage by harmine and 9-methyl-harmine
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DOI：
10.1016/j.jphotobiol.2014.01.020
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发表时间：
2014-03-05
影响因子：
5.4
通讯作者：
Cabrerizo, Franco M.
中科院分区：
文献类型：
--
作者：
Vignoni, Mariana;Erra-Balsells, Rosa;Cabrerizo, Franco M.
已知β-咔啉能够在游离DNA中产生光敏损伤，但关于其对细胞DNA的影响的信息很少。因此，我们分析了去氢骆驼蓬碱和9-甲基-去氢骆驼蓬碱在UVA照射下对V79细胞的DNA损伤，以及相关的微核和光毒性的产生。结果表明，在细胞DNA中产生的最常见的光产物是修饰的嘌呤，如8-氧代-7，8-二氢鸟嘌呤。仅观察到相对较少的单链断裂。CPD是不存在的，虽然它们是在相同条件下照射的无细胞DNA中产生的。细胞中DNA损伤的总体程度明显小于在游离DNA中观察到的程度。细胞DNA损伤的产生与显著的微核产生和细胞增殖降低相关。数据表明β-咔啉在哺乳动物细胞中充当光敏剂。DNA修饰的范围，以及因此DNA损伤产生的机制，与用无细胞DNA观察到的有很大不同。(C)2014爱思唯尔有限公司版权所有。
It is known that beta-carbolines are able to produce photosensitized damage in cell-free DNA, but there is little information on their effects on cellular DNA. Therefore, we have analyzed the DNA damage produced by harmine and 9-methyl-harmine under UVA irradiation in V79 cells, together with the associated generation of micronuclei and photocytotoxicity. The results indicate that the most frequent photoproducts generated in the cellular DNA are modified purines such as 8-oxo-7,8-dihydroguanine. Only relatively few single-strand breaks were observed. CPDs were absent, although they were generated in cell-free DNA irradiated under the same conditions. The overall extent of DNA damage in the cells was considerably smaller than the one observed in cell free DNA. The generation of cellular DNA damage was associated with a significant generation of micronuclei and decreased cell proliferation. The data indicate that beta-carbolines act as photosensitizers in mammalian cells. The spectrum of DNA modification, and therefore the mechanism of DNA damage generation, differs considerably from that observed with cell-free DNA. (C) 2014 Elsevier B.V. All rights reserved.