Elevated α/β ratio after hypofractionated radiotherapy correlated with DNA damage repairment in an experimental model of prostate cancer.

IF 1.9 4区 医学 Q2 BIOLOGY Journal of Radiation Research Pub Date : 2024-10-28 DOI:10.1093/jrr/rrae077
Ming Cui, Yuexian Li, Ji Liu, Deyu Sun
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Abstract

Our previous study demonstrated that the linear quadratic model appeared to be not well-suited for high dose per fraction due to an observed increase in α/β ratio as the dose per fraction increased. To further validate this conclusion, we draw the cell survival curve to calculate the α/β ratio by the clone formation experiment and then convert the fractionated radiation dose into an equivalent single hypofractionated radiation dose comparing with that on the survival curve. Western Blot and laser confocal immunofluorescence were used to detect the expression of γ-H2AX and RAD51 after different fractionated modes of radiation. We constructed a murine xenograft model, and changes in transplanted tumor volume were used to evaluate the biological effects after different fractionated radiation. The results demonstrated that when fractionated radiation dose was converted into equivalent single hypofractionated radiation dose, the effectiveness of hypofractionated radiation was overestimated. If a larger α/β ratio was used, the discrepancy tended to become smaller. γ-H2AX was higher in 24 h after a single high dose radiation than the continuous expression of the DNA repair marker RAD51. This implies more irreparable damage in a single high dose radiation compared with fractionated radiation. In the murine xenograft model, the effectiveness of hypofractionated radiation was also overestimated, and additional fractions of irradiation may be required. The conclusion is that after single hypofractionated radiation, the irreparable damage in cells increased (α value increased) and some repairable sublethal damage (β value) was converted into irreparable damage (α value). When α value increased and β value decreased, the ratio increased.

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在前列腺癌实验模型中,低剂量放疗后α/β比值升高与DNA损伤修复相关。
我们之前的研究表明,线性二次模型似乎并不适合高分次剂量,因为随着分次剂量的增加,α/β比值也会增加。为了进一步验证这一结论,我们绘制了细胞存活曲线,通过克隆形成实验计算α/β比值,然后将分次辐射剂量转换为等效的单次低分次辐射剂量,并与存活曲线上的比值进行比较。采用 Western Blot 和激光共聚焦免疫荧光技术检测不同分次辐射模式后γ-H2AX 和 RAD51 的表达。我们构建了小鼠异种移植模型,并利用移植肿瘤体积的变化来评估不同分次辐射后的生物学效应。结果表明,将分次放射剂量转换为等效的单次低分次放射剂量时,低分次放射的有效性被高估。如果使用更大的α/β比值,差异则有变小的趋势。单次高剂量辐射后 24 小时内,γ-H2AX 的表达高于 DNA 修复标记 RAD51 的持续表达。这意味着与分次辐射相比,单次大剂量辐射造成的不可修复的损伤更大。在小鼠异种移植模型中,低分次辐射的有效性也被高估,可能需要额外的分次照射。结论是单次低分次辐射后,细胞内不可修复的损伤增加(α 值增加),一些可修复的亚致死性损伤(β 值)转化为不可修复的损伤(α 值)。当 α 值增大而 β 值减小时,比值增大。
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来源期刊
CiteScore
3.60
自引率
5.00%
发文量
86
审稿时长
4-8 weeks
期刊介绍: The Journal of Radiation Research (JRR) is an official journal of The Japanese Radiation Research Society (JRRS), and the Japanese Society for Radiation Oncology (JASTRO). Since its launch in 1960 as the official journal of the JRRS, the journal has published scientific articles in radiation science in biology, chemistry, physics, epidemiology, and environmental sciences. JRR broadened its scope to include oncology in 2009, when JASTRO partnered with the JRRS to publish the journal. Articles considered fall into two broad categories: Oncology & Medicine - including all aspects of research with patients that impacts on the treatment of cancer using radiation. Papers which cover related radiation therapies, radiation dosimetry, and those describing the basis for treatment methods including techniques, are also welcomed. Clinical case reports are not acceptable. Radiation Research - basic science studies of radiation effects on livings in the area of physics, chemistry, biology, epidemiology and environmental sciences. Please be advised that JRR does not accept any papers of pure physics or chemistry. The journal is bimonthly, and is edited and published by the JRR Editorial Committee.
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