DNA damage detected with gammaH2AX in endometrioid adenocarcinoma cell lines.
DNA damage detected with gammaH2AX in endometrioid adenocarcinoma cell lines.
复制标题
DOI：
10.3892/ijo_00000589
复制
发表时间：
2010-05
影响因子：
5.2
通讯作者：
Sawai T
中科院分区：
文献类型：
--
作者：
Ikeda M;Kurose A;Takatori E;Sugiyama T;Traganos F;Darzynkiewicz Z;Sawai T
组蛋白H_2AX(γH_2AX)的磷酸化是DNA损伤的敏感标志，尤其是诱导DNA双链断裂。用多参数流式细胞术检测阿霉素、顺铂和5-氟尿嘧啶对四种子宫内膜样腺癌细胞株(HEC-1A、HEC-1B、Ishikawa、KLE)的作用，发现药物诱导的磷酸化H_2AX(γH_2AX)升高与细胞周期、诱导细胞凋亡和诱导细胞衰老有关，β-半乳糖苷酶分析检测了后者。研究表明，不同细胞系在药物处理后DNA损伤与细胞周期时相特异性、诱导细胞凋亡或衰老方面的影响存在显著差异。DOX对γH_2AX的诱导作用没有表现出明显的细胞周期特异性，其作用机制可能与其他因素调节的氧化损伤有关。顺铂和5-FU处理后，S期细胞中H_2AX优先被磷酸化，这与复制应激的诱导是一致的。与其他细胞系相比，表达wtP53的Ishikawa细胞的反应不同。这些数据表明，使用这些药物治疗子宫内膜样腺癌可能必须针对个别患者进行定制。流式细胞术对γ、H_2AX和DNA含量的双变量分析对于更好地了解抗肿瘤药物的效果是一项有用的技术，并可能有助于定制患者的治疗。
Phosphorylation of histone H2AX (γH2AX) is a sensitive marker of DNA damage, particularly induction of DNA double-strand breaks. Using multiparameter cytometry we explored the effects of doxorubicin (DOX), cisplatin (CDDP) and 5-fluorouracil (5-FU) on four types of endometrioid adenocarcinoma cell lines (HEC-1A, HEC-1B, Ishikawa, KLE) correlating the drug-induced increases in phosphorylated H2AX (γH2AX) with cell cycle phase, induction of apoptosis and induction of cell senescence, the latter detected by analysis of β-galactosidase. The study revealed significant differences among the cell lines in the effects of DNA damage vis-a-vis cell cycle phase specificity, induction of apoptosis or senescence following drug treatment. DOX treatment showed little cell cycle specificity in terms of induction of γH2AX, and its mechanism, which is similar to another anthracycline DNA topoisomerase II inhibitor mitoxantrone, may involve oxidative DNA damage modulated by other factors. Treatment with CDDP and 5-FU led to phosphorylation of H2AX preferentially in S-phase cells, consistent with the induction of replication stress. The response of Ishikawa cells expressing wt p53 was different compared to other cell lines. The data suggest that the treatment of endometrioid adenocarcinoma with these drugs may have to be customized to individual patients. The flow cytometric bivariate analysis of γH2AX and DNA content is a useful technique for better understanding the effects of antitumor agents and may contribute to customized patient treatments.
登录
查看更多内容
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
DOI：
10.1073/pnas.0830918100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Rothkamm, K;Löbrich, M
通讯作者：
Löbrich, M
影响因子：
11.4
作者：
Stiff, Thomas;Walker, Sarah A.;Jeggo, Penny A.
通讯作者：
Jeggo, Penny A.
影响因子：
3.7
作者：
Kurose, A;Tanaka, T;Darzynkiewicz, Z
通讯作者：
Darzynkiewicz, Z
影响因子：
8.8
作者：
Yang, X.;Fraser, M.;Abedini, M. R.;Bai, T.;Tsang, B. K.
通讯作者：
Tsang, B. K.