Are platinum agents, paclitaxel and irinotecan effective for clear cell carcinoma of the ovary? DNA damage detected with γH2AX induced by anticancer agents.
Are platinum agents, paclitaxel and irinotecan effective for clear cell carcinoma of the ovary? DNA damage detected with γH2AX induced by anticancer agents.
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DOI：
10.1186/1757-2215-5-16
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发表时间：
2012-06-12
影响因子：
4
通讯作者：
Sugiyama T
中科院分区：
文献类型：
--
作者：
Takatori E;Shoji T;Kumagai S;Sawai T;Kurose A;Sugiyama T
本文用γ H_2AX检测了两种卵巢透明细胞癌（CCC）细胞系在抗肿瘤药物诱导下DNA损伤的发生率和类型的差异。使用卵巢透明细胞癌培养细胞系（OVISE和RMG-1）检测抗癌剂CDDP、CBDCA、PTX和SN-38的抗肿瘤活性。培养后，用各抗癌剂处理各细胞系，收集细胞，固定，然后与抗γ H2 AX抗体反应。用流式细胞仪分别检测γ H2 AX和核DNA，以确定γ H2 AX在细胞周期各时相的表达。CDDP作用后，S期细胞DNA损伤明显，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CBDCA的敏感性不同。PTX的抗肿瘤作用是通过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。本研究中使用的免疫细胞化学方法检测γ H2 AX，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。
Differences in the incidences and types of DNA damage induced by antitumor agents for clear cell carcinoma (CCC) were determined in 2 ovarian CCC cell lines using γH2AX. The antitumor activity of anticancer agents, CDDP, CBDCA, PTX and SN-38, was examined using ovarian clear cell carcinoma cultured cell lines (OVISE and RMG-I). After culture, each cell line was treated with each anticancer agent, the cells were collected, fixed, and then reacted with the anti-γH2AX antibody. γH2AX and nuclear DNA were then simultaneously detected by flow cytometry using FITC and propidium iodide, respectively, to determine γH2AX in each cell cycle phase. After administration of 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 CBDCA differed between the two cell lines. The antitumor effect of 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 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.
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影响因子：
1.6
作者：
Dickey JS;Redon CE;Nakamura AJ;Baird BJ;Sedelnikova OA;Bonner WM
通讯作者：
Bonner WM
DOI：
10.1111/j.1349-7006.2002.tb01312.x
发表时间：
2002-06
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Itamochi H;Kigawa J;Sultana H;Iba T;Akeshima R;Kamazawa S;Kanamori Y;Terakawa N
通讯作者：
Terakawa N
影响因子：
5.3
作者：
Fragkos, Michalis;Jurvansuu, Jaana;Beard, Peter
通讯作者：
Beard, Peter
影响因子：
4.7
作者：
Ho, ESC;Lai, CR;Liu, FS
通讯作者：
Liu, FS
影响因子：
3.3
作者：
Takano, Masashi;Sugiyama, Toru;Kikuchi, Yoshihiro
通讯作者：
Kikuchi, Yoshihiro