Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays
Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays
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DOI：
10.1111/j.1349-7006.2009.01082.x
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发表时间：
2009-04-01
期刊：
影响因子：
5.7
通讯作者：
Fukumoto, Manabu
中科院分区：
文献类型：
--
作者：
Kuwahara, Yoshikazu;Li, Li;Fukumoto, Manabu
放射治疗是根除恶性肿瘤的主要治疗手段之一。然而，放射抵抗细胞的存在仍然是放疗和放化疗的最关键障碍之一。用于肿瘤治疗的标准放射疗法包括大约2戈伊，每天一次，每周5天，持续5-8周。为了了解放射抗性细胞的特征并开发更有效的放射治疗，我们通过长期分次暴露于2戈伊的X射线，从亲本HepG 2细胞建立了一种新的具有临床意义的放射抗性细胞系HepG 2 -8960-R。每天暴露于2戈伊X射线超过30天，HepG 2 -8960-R细胞继续增殖，而所有亲本HepG 2细胞停止增殖。在暴露于分次2戈伊X射线后，HepG 2 -8960-R中的微核和γ-H2 AX残留灶的诱导频率低于HepG 2。流式细胞术分析显示，HepG 2 -8960-R中细胞周期的S期和G2/M期细胞的比例高于HepG 2。这些表明，临床相关的辐射抗性（CRR）细胞的反应，以分次辐射不仅仅是一个累积的反应，每一个分次辐射。这是第一个从同基因亲本细胞系建立CRR细胞系的报告。（Cancer Sci 2009; 100：747-752）
Radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors. However, the existence of radioresistant cells remains one of the most critical obstacles in radiotherapy and radiochemotherapy. Standard radiotherapy for tumor treatment consists of approximately 2 Gy once a day, 5 days a week, over a period of 5-8 weeks. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we established a novel radioresistant cell line, HepG2-8960-R with clinical relevance from parental HepG2 cells by long-term fractionated exposure to 2 Gy of X-rays. HepG2-8960-R cells continued to proliferate with daily exposure to 2 Gy X-rays for more than 30 days, while all parental HepG2 cells ceased. After exposure to fractionated 2 Gy X-rays, induction frequencies of micronuclei and remaining foci of gamma-H2AX in HepG2-8960-R were less than those in HepG2. Flow cytometric analysis revealed that the proportion of cells in S-and G2/M-phase of the cell cycle was higher in HepG2-8960-R than in HepG2. These suggest that the response of clinically relevant radioresistant (CRR) cells to fractionated radiation is not merely an accumulated response to each fractionated radiation. This is the first report on the establishment of a CRR cell line from an isogenic parental cell line. (Cancer Sci 2009; 100: 747-752)