Characterization of DNA damage induced by 3,4-estrone-o-quinone in human cells.
Characterization of DNA damage induced by 3,4-estrone-o-quinone in human cells.
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DOI：
10.1016/s0021-9258(18)55309-6
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发表时间：
1991-09
期刊：
影响因子：
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通讯作者：
L. M. Nutter;E. Ngo;Yusuf J. Abul-Hajj
中科院分区：
文献类型：
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作者：
L. M. Nutter;E. Ngo;Yusuf J. Abul-Hajj
已经对用 1,5 (10)-雌二烯-3,4,17-三酮（3,4-雌酮-o-醌；3,4-EQ）处理的人乳腺癌细胞系诱导的 DNA 损伤进行了定性和定量测量。用 3,4-EQ 处理的 MCF-7 细胞中形成单链 (ss) DNA 断裂，但未形成双链 (ds) DNA 断裂。将细胞在不含 3,4-EQ 的培养基中孵育 2 小时和 4 小时后，MCF-7 细胞中形成的 ss DNA 断裂得到部分修复（即与暴露于 3,4-EQ 1 小时且没有恢复期的细胞中的 ss DNA 断裂相比，分别修复 33% 和 23%）。在暴露于双功能烷化剂丝裂霉素 C 的 MCF-7 细胞中，证明了链间 DNA 交联的形成，但在暴露于 3,4-EQ 的细胞中则不然。暴露于喜树碱和依托泊苷后，在 MCF-7 细胞中检测到蛋白连接的 DNA 断裂，但未检测到 3,4-EQ，这表明 3,4-EQ 诱导的 ss DNA 断裂不太可能是通过拓扑异构酶介导的。在雌激素受体阴性细胞系 BT-20 暴露于 3,4-EQ 后，检测到 ss DNA 断裂的诱导。此外，培养基中过量的雌二醇并不能阻止 3,4-EQ 诱导的 ss DNA 断裂，表明 DNA 损伤不是通过雌激素受体介导的。在 ss DNA 断裂测定中对新合成的醌类似物 5,6,7,8-四氢-1-2-萘醌的评估表明，3,4-EQ 的 A 和 B 环部分足以在 MCF-7 细胞中产生 ss DNA 断裂。
The DNA damage induced in a human breast cancer cell line treated with 1,5 (10)-estradiene-3,4,17-trione (3,4-estrone-o-quinone; 3,4-EQ) has been measured qualitatively and quantitatively. Single-strand (ss) but not double-strand (ds) DNA breaks were formed in MCF-7 cells treated with 3,4-EQ. The ss DNA breaks formed in MCF-7 cells were partially repaired after incubation of cells in 3,4-EQ-free media for 2 and 4 h (i.e. 33 and 23% repair, respectively, as compared to the ss DNA breaks in cells after a 1-h exposure to 3,4-EQ without a recovery period). The formation of interstrand DNA cross-links was demonstrated in MCF-7 cells exposed to the bifunctional alkylating agent, mitomycin C, but not in those exposed to 3,4-EQ. Protein-linked DNA breaks were detected in MCF-7 cells after exposure to camptothecin and etoposide but not 3,4-EQ, suggesting that the ss DNA breaks induced by 3,4-EQ are unlikely to be mediated via topoisomerases. The induction of ss DNA breaks was detected in the estrogen receptor-negative cell line, BT-20, after exposure to 3,4-EQ. Furthermore, excess estradiol in culture media did not prevent 3,4-EQ-induced ss DNA breaks, suggesting that the DNA damage was not mediated via the estrogen receptor. Evaluation of the newly synthesized quinone analogue, 5,6,7,8-tetrahydro-1-2-naphthoquinone, in the ss DNA breakage assay revealed that the A and B ring moiety of 3,4-EQ is sufficient to produce ss DNA breaks in MCF-7 cells.