Hydantoin derivative formation from oxidation of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) and incorporation of 14C-labeled 8-oxodG into the DNA of human breast cancer cells
Hydantoin derivative formation from oxidation of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) and incorporation of 14C-labeled 8-oxodG into the DNA of human breast cancer cells
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DOI：
10.1016/j.bmcl.2005.05.113
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发表时间：
2005-08-01
影响因子：
2.7
通讯作者：
Henderson, PT
中科院分区：
文献类型：
--
作者：
Hah, SS;Kim, HM;Henderson, PT
7,8-二氢-8-氧代-2'-脱氧鸟苷 (8-oxodG) 的单电子氧化产生了胍基乙内酰脲衍生物 (dGh) 和螺亚氨基二乙内酰脲衍生物 (dSp)，这两种物质均被认为是可能在体内形成的诱变产物。无论 pH 值如何，核苷 dGh 是室温下的主要产物。结果与先前发表的使用 2,3',5'-三乙酰氧基-8-氧代-7,8-二氢鸟苷的模型研究相反（Luo, W.；Miller, J.G.；Rachlin, E. M.；Burrows, C. J. Org. Lett. 2000, 2, 613；Luo, W.；Miller, J.G.；Rachlin, E.M.；Burrows, C.J. Chem. Res. 2001, 14, 927），他观察到在中性 pH 条件下螺亚氨基二乙内酰脲衍生物是主要产物。显然，连接到 8-oxodG 核糖部分的官能团影响核碱基衍生物的氧化化学。为了在体内探索这种化学反应，合成了 C-14 标记的 8-oxodG，并与生长中的 MCF-7 人乳腺癌细胞一起孵育，结果通过新型加速器质谱分析检测到该化合物掺入细胞 DNA 中。 (c) 2005 Elsevier Ltd. 保留所有权利。
One-electron oxidation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) yielded a guanidinohydantoin derivative (dGh) and a spiroiminodihydantoin derivative (dSp), both putatively mutagenic products that may be formed in vivo. The nucleoside dGh was the major product at room temperature, regardless of pH. The results are contrary to previously published model studies using 2,3',5'-triacetoxy-8-oxo-7,8-dihydroguanosine (Luo, W.; Miller, J.G.; Rachlin, E. M.; Burrows, C. J. Org. Lett. 2000, 2, 613; Luo, W.; Miller, J.G.; Rachlin, E.M.; Burrows, C.J. Chem. Res. Toxicol. 2001, 14, 927), who observed a spiroiminodihydantoin derivative as the major product at neutral pH. Clearly, the functional groups attached to the ribose moiety of 8-oxodG influence the oxidation chemistry of the nucleobase derivative. To explore this chemistry in vivo, C-14-labeled 8-oxodG was synthesized and incubated with growing MCF-7 human breast cancer cells, resulting in the incorporation of the compound into cellular DNA as measured by a novel accelerator mass spectrometry assay. (c) 2005 Elsevier Ltd. All rights reserved.