电离辐射诱导的人皮肤原代黑色素细胞和角化细胞DNA损伤反应。

IF 1.7 4区 生物学 Q4 CELL BIOLOGY
Jarah A Meador, Rebecca J Morris, Adayabalam S Balajee
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引用次数: 1

摘要

目前,我们对组织微环境中不同类型的细胞如何响应低和高线性能量转移(LET)辐射的了解非常有限。在本研究中,比较分析了γ射线诱导的人类原代黑色素细胞和角化细胞的DNA损伤和修复。我们的研究表明,在自发和电离辐射(IR)诱导的53BP1病灶形成和持久性方面,黑素细胞和角化细胞都存在适度的个体间变异性。总的来说,在不同剂量的γ射线(0.1-2.5 Gy)照射后,黑色素细胞的53BP1灶诱导值比角质形成细胞略高(1.66-2.79倍)。为了验证ATM激酶对ir诱导的53BP1病灶形成的影响,在辐射前用特异性ATM激酶抑制剂(KU55993, 10 μM)处理黑色素细胞和角质形成细胞1小时。ATM激酶抑制导致所有3个供体的黑色素细胞和角化细胞中自发和ir诱导的53BP1病灶减少17-42%。在不同暴露时间(6小时和24小时)后,在ATM抑制的黑素细胞和角质形成细胞中观察到ir诱导的53BP1焦点数的持久性增加。综上所述,我们的研究表明,黑素细胞和角质形成细胞中DNA双链断裂(DSB)的诱导和修复存在个体间差异,ATM对两种人类皮肤细胞类型的最佳DSB修复效率至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ionizing Radiation-Induced DNA Damage Response in Primary Melanocytes and Keratinocytes of Human Skin.

Currently, our knowledge of how different cell types in a tissue microenvironment respond to low and high linear energy transfer (LET) radiation is highly restricted. In this study, a comparative analysis was performed on γ-ray-induced DNA damage and repair in primary human melanocytes and keratinocytes isolated from 3 donors. Our study demonstrates a modest interindividual variability in both melanocytes and keratinocytes in terms of both spontaneous and ionizing radiation (IR)-induced 53BP1 foci formation and persistence. Melanocytes, in general, showed a slightly elevated (1.66-2.79 folds more) 53BP1 foci induction relative to keratinocytes after exposure to different doses of γ-rays (0.1-2.5 Gy) radiation. To verify the influence of ATM kinase on IR-induced 53BP1 foci formation, melanocytes and keratinocytes were treated with a specific ATM kinase inhibitor (KU55993, 10 μM) for 1 h prior to radiation. ATM kinase inhibition resulted in the reduction of both spontaneous and IR-induced 53BP1 foci by 17-42% in both melanocytes and keratinocytes of all the 3 donors. Increased persistence of IR-induced 53BP1 foci number was observed in ATM-inhibited melanocytes and keratinocytes after different post exposure times (6 h and 24 h). Taken together, our study suggests that interindividual variations exist in the induction and repair of DNA double-strand breaks (DSBs) in melanocytes and keratinocytes and that ATM is crucial for an optimal DSB repair efficiency in both human skin cell types.

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来源期刊
Cytogenetic and Genome Research
Cytogenetic and Genome Research 生物-细胞生物学
CiteScore
3.10
自引率
5.90%
发文量
25
审稿时长
1 months
期刊介绍: During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.
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