DNA damage detected with γH2AX induced by anticancer drugs on ovarian clear cell carcinoma

采用组蛋白希斯顿H2 AX（γ H2 AX）磷酸化方法，比较卵巢透明细胞癌（CCC）、子宫体类腺瘤和宫颈鳞状细胞癌抗肿瘤药物诱导的DNA损伤的发生率和类型的差异.卵巢透明细胞腺癌（CCC）：顺铂（CDDP）作用后，S期细胞DNA损伤频繁，G1期和G2/M期细胞周期阻滞，γ H2 AX无明显增加。两种细胞系对CDDP和卡铂（CBDCA）的敏感性不同。紫杉醇（PTX）的抗肿瘤作用是由G2/M期阻滞诱导的，与CBDCA联合治疗，诱导G2/M期细胞的DNA损伤，可能是有效的。这是日本首次以γ H2 AX为指标，通过关注细胞周期与DNA损伤之间的关系，评价抗癌药物的抗肿瘤活性的研究。免疫细胞化学方法用于 关于我们 本研究检测γ H2 AX，其即使在非常低的浓度下也能以高灵敏度指示DNA损伤。因此，一个有前途的方法，容易和快速地确定代理可能有效地对CCC。2.子宫体子宫内膜样腺癌：研究显示，药物治疗后，细胞系之间在DNA损伤与细胞周期特异性、诱导凋亡或衰老方面存在显著差异。多柔比星（DOX）对γ H2 AX的诱导作用不具有细胞周期特异性，其机制与另一种蒽环类DNA拓扑异构酶II抑制剂米托蒽醌相似，可能涉及其他因素调控的氧化性DNA损伤。用CDDP和5-氟尿嘧啶（5-FU）处理导致在S期细胞中优先磷酸化H2 AX，这与复制应激的诱导一致。表达wt p53的石川细胞的反应与其他细胞系相比是不同的。这些数据表明，用这些药物治疗类腺癌可能必须根据个体患者的情况进行定制。少

Differences in the incidences and types of DNA damage induced by antitumor agents for clear cell carcinoma (CCC) of the ovary, endometrioid adenocar cinoma of the uterine corpus, and squamous cell carcinoma of the cervix were determined using phosphory- lation of histon H2AX (γH2AX).1. Clear cell adenocarcinoma of the ovary (CCC): After administration of cisplatin(CDDP), DNA damage was frequent in S -phase cells, while cell-cycle arrest occurred in the G1 and G2/M phases and γH2AX did not increase in CDDP-resistant cells. Sensitivities to CDDP and carboplatin(CBDCA) differed between the two cell lines. The antitumor effect of paclitaxel(PTX) is induced by G2/M arrest, and combination treatment with CBDCA, inducing DNA damage in G2/M-phase cells, might be effective.This is the first study in Japan to evaluate the antitumor activity of anticancer agents by focusing on the relationship between the cell cycle and DNA damage using γH2AX as an indicator. The immunocytochemical method used in … More this study detects γH2AX, which indicates DNA damage even at very low concentrations and with high sensitivity. Therefore, a promising method of easily and rapidly identifying agents potentially effective against CCC. 2.Endometrioid adenocarcinoma of the uterine corpus: The study revealed significant differences among the cell lines in the effects of DNA damage vis-a-vis cell cycle phasespecificity, induction of apoptosis or senescence following drug treatment. doxorubicin (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-fluorouracil (5-FU) led to phosphorylation of H2AXpreferentially 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. Less