在低剂量电离辐射下预测DNA损伤信号.
Jeong-In Park1, Seung-Youn Jung1, Kyung-Hee Song1
1Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
International journal of molecular medicine
|May 2, 2024
概括
研究人员确定了参与DNA修复和细胞周期调节的关键分子,作为低剂量辐射暴露的敏感标记物. 这些对辐射敏感的标记物显示出预测暴露和评估人类风险的前景.
科学领域:
- 生物医学科学 生物医学科学
- 辐射生物学 辐射生物学
- 分子生物学分子生物学
背景情况:
- 开发可靠的辐射反应生物标志物对于准确的评估至关重要.
- 现有的方法在辐射研究中往往缺乏广泛的应用.
- 识别低剂量辐射的敏感标记是一个重大挑战.
研究的目的:
- 识别和验证用于低剂量辐射敏感性的新生物标志物.
- 研究DNA损伤修复,细胞循环调节和细胞因子信号分子的作用.
- 探索潜在的辐射保护剂及其机制.
主要方法:
- 分析公共数据库以选择候选分子.
- 细胞系 (HuT 78,IM-9) 和人类外周血液单核细胞的辐射.
- 西部斑点分析以评估蛋白质表达和激活 (ATM,CHK2,p53,H2AX).
- 在体内对小鼠进行的研究,以评估 cinobufagin 的辐射保护作用.
- 使用特定抑制剂 (KU60019,BML-277,pifithrin-α,nutlin-3a) 评估细胞亡和调节辐射诱导的细胞死亡.
主要成果:
- 在照射后,ATM,CHK2,p53和H2AX的激活以度依赖的方式增加.
- 奇诺布法根在小鼠中显示出对辐射保护作用的趋势,增加骨髓细胞和存活率.
- BML-277降低了辐射诱导的p-CHK2和γH2AX水平,减轻了亡.
结论:
- 参与DNA损伤修复和细胞循环调节的精选分子作为有希望的低剂量辐射敏感标记物.
- 这些标记可以帮助预测辐射暴露和评估相关的人类健康风险.
- 该研究为开发针对辐射反应通路的新候选药物提供了基础.
相关概念视频
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
Mutations
37.0K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
37.0K
Overview of DNA Repair
31.0K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.0K
DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
Biological Effects of Radiation
15.4K
All radioactive nuclides emit high-energy particles or electromagnetic waves. When this radiation encounters living cells, it can cause heating, break chemical bonds, or ionize molecules. The most serious biological damage results when these radioactive emissions fragment or ionize molecules. For example, α and β particles emitted from nuclear decay reactions possess much higher energies than ordinary chemical bond energies. When these particles strike and penetrate matter, they...
15.4K
Fixing Double-strand Breaks
12.6K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.6K


