已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

相对生物效应 辐射敏感性 克隆形成试验 医学 范科尼贫血 线性能量转移 质子 辐照 癌症研究 癌症 核医学 细胞培养 布拉格峰 放射生物学 DNA修复 放射治疗 DNA 生物 内科学 遗传学 物理 核物理学 量子力学
作者
Qi Liu,Priyanjali Ghosh,Nicole Magpayo,M Testa,Shikui Tang,Liliana Gheorghiu,Peter J. Biggs,Harald Paganetti,Jason A. Efstathiou,Hsiao‐Ming Lu,Kathryn D. Held,Henning Willers
出处
期刊:International Journal of Radiation Oncology Biology Physics [Elsevier BV]
卷期号:91 (5): 1081-1089 被引量:87
标识
DOI:10.1016/j.ijrobp.2014.12.046
摘要

Purpose Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and 137Cs γ-rays were used. To estimate the RBE of protons relative to 60Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation. Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and 137Cs γ-rays were used. To estimate the RBE of protons relative to 60Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
jacob258完成签到 ,获得积分10
1秒前
刘宇萌完成签到 ,获得积分10
3秒前
4秒前
lvsehx发布了新的文献求助10
4秒前
YOLO完成签到 ,获得积分10
8秒前
Legend_完成签到 ,获得积分10
8秒前
9秒前
9秒前
kelien1205完成签到 ,获得积分10
10秒前
多年以后发布了新的文献求助20
11秒前
左肩微笑发布了新的文献求助10
11秒前
锅包肉爱吃肉完成签到 ,获得积分10
12秒前
顺顺科研完成签到 ,获得积分10
12秒前
牛蛙丶丶完成签到,获得积分10
13秒前
Grandir发布了新的文献求助20
13秒前
hjy完成签到,获得积分10
13秒前
14秒前
meimei完成签到 ,获得积分10
15秒前
15秒前
wenhao完成签到 ,获得积分10
15秒前
刺闰土的猹完成签到,获得积分10
15秒前
99668完成签到,获得积分10
16秒前
可爱的函函应助直觉采纳,获得10
17秒前
麦子发布了新的文献求助10
18秒前
左肩微笑完成签到,获得积分20
19秒前
在水一方应助笔墨留香采纳,获得10
19秒前
璨澄完成签到 ,获得积分10
20秒前
天天快乐应助Li采纳,获得10
20秒前
桀桀桀完成签到,获得积分10
21秒前
简单白风完成签到 ,获得积分10
23秒前
23秒前
青糯完成签到 ,获得积分10
23秒前
清爽的火车完成签到 ,获得积分10
23秒前
ganson完成签到 ,获得积分10
25秒前
25秒前
26秒前
Bismarck完成签到,获得积分20
27秒前
28秒前
28秒前
楚楚完成签到 ,获得积分10
28秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
Aktuelle Entwicklungen in der linguistischen Forschung 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989957
求助须知:如何正确求助?哪些是违规求助? 3532034
关于积分的说明 11255966
捐赠科研通 3270856
什么是DOI,文献DOI怎么找? 1805053
邀请新用户注册赠送积分活动 882252
科研通“疑难数据库(出版商)”最低求助积分说明 809216