Different roles of Fpg and Endo III on catechol-induced DNA damage in extended-term cultures of human lymphocytes and L5178Y mouse lymphoma cells
Different roles of Fpg and Endo III on catechol-induced DNA damage in extended-term cultures of human lymphocytes and L5178Y mouse lymphoma cells
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DOI：
10.1016/j.tiv.2005.04.011
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发表时间：
2005-09-01
影响因子：
3.2
通讯作者：
Hellman, BE
中科院分区：
文献类型：
--
作者：
Andersson, MA;Hellman, BE
儿茶酚是一种基因毒性物质，被认为通过氧化途径诱导DNA损伤。利用彗星实验和修复特异性酶甲氨基嘧啶糖基化酶（Fpg）和核酸内切酶III (Endo 111)，我们检测了儿茶酚在人淋巴细胞和小鼠淋巴瘤细胞的长期培养中诱导DNA损伤的能力。我们的研究结果表明，小鼠淋巴瘤细胞对儿茶酚诱导的DNA损伤比长期培养的人类淋巴细胞更敏感。在高浓度下，儿茶酚诱导的损伤似乎独立于Fpg和Endo 111，可能表明DNA损伤的非氧化途径（例如，涉及大体积加合物）。事实上，Endo 111而不是Fpg增强了儿茶酚对DNA的破坏作用，这表明苯的代谢物要么介导嘧啶的氧化，而不是嘌呤的氧化，要么氧化的嘌呤修复得更有效，至少在人类淋巴细胞中是这样。在后者的细胞中，发现低浓度的儿茶酚可以减少DNA的迁移。考虑到Fpg的作用及其对8-氧鸟嘌呤的加合物特异性检测，这表明低浓度儿茶酚具有降低氧化嘌呤背景水平的抗氧化作用。(c) 2005 Elsevier Ltd版权所有。
Catechol is a genotoxic agent assumed to induce DNA damage via the oxidative pathway. Using the comet assay and the repair-specific enzymes formamido pyrimidine glycosylase (Fpg) and endonuclease III (Endo 111), we examined the ability of catechol to induce DNA damage in extended-term cultures of human lymphocytes and mouse lymphoma cells. Our results suggest that mouse lymphoma cells are somewhat more sensitive towards catechol-induced DNA damage than the extended-term cultures of human lymphocytes. At high concentrations, the catechol-induced damage seemed to be independent of both Fpg and Endo 111, possibly indicating a non-oxidative pathway for the DNA damage (involving, for example, a bulky adduct). The fact that Endo 111, but not Fpg, enhanced the DNA damaging effect of catechol, suggests that this metabolite of benzene either mediates oxidation of pyrimidines rather than purines, or that oxidised purines are repaired more efficiently, at least in human lymphocytes. In the latter cells, low concentrations of catechol were found to reduce the DNA migration. Considering the role of Fpg and it's adduct specific detection of 8-oxoguanine, this suggests that a low concentration of catechol has an antioxidative effect reducing the background levels of oxidized purines. (c) 2005 Elsevier Ltd. All rights reserved.