加速重离子辐射对水稻的生物学效应研究——Ⅰ.加速重离子及~(60)Coγ射线辐照水稻干种子的当代生物学效应

用高传能线密度(LET)的~(56)Fe(190keV/μ)、~(40)Ar(90keV/μ)离子束及低LET的~(60)Coγ射线(0.27keV/μ)照射水稻干种子,对当代幼苗生长、根尖微核细胞率和染色体畸变率的效应,进行了实验分析。结果表明:对比三种辐射源,微核细胞率与染色体畸变率均随处理剂量增加而增加,且呈线性关系。以幼苗的生长半抑制剂量(D_(50))为指标,三种电离辐射(~(56)Fe、~(40)Ar离子束和~(60)Coγ射线)的相对生物学效应(RBE)比值为6.3∶1.9∶1。以微核细胞率为指标,三者的RBE比较值为11∶4∶1。可见高LET的~(56)Fe和~(40)Ar比低LET的~(60)Co有较高的辐射生物学效应,尤其是在诱发细胞核染色体畸变和微核出现方面,高LET离子束有很高的效率。     

质子治疗对细胞自由基产额影响的蒙特卡罗模拟计算

随着质子FLASH治疗等新兴放疗技术的发展,细胞受辐照后生物学效应的不确定性成为急需解决的难题。由于缺乏对物理-化学阶段机理的完整理解,目前的模拟工作仍然以调整化学参数使自由基产额与实验数据相匹配为主。作为一个不断发展的蒙特卡罗软件,Geant4能够在纳米尺度上模拟入射粒子在短时间内通过物理和化学相互作用引起水分子辐解的过程。基于Geant4软件构建了一个简易的细胞模型,模拟了细胞靶体内自由基产额受辐射粒子影响的情况,并对靶内自由基产额的变化趋势进行了详细计算。研究表明,随着LET的逐渐增大,自由基OH^·的数目占比从25%下降到10%左右。当考虑质子FLASH透射治疗时,使用25%的自由基OH^·数目占比作为化学损伤参数去评估细胞DNA损伤将会更为合理。同时,两种活性氧自由基O₂^·和O₂^-在超高剂量率下的产额G(t)随模拟时间的发展都出现了不同程度的升高。研究结果阐明了不同治疗深度下细胞靶体内自由基产额随时间和粒子能量的变化情况,揭示了模拟工作中质子FLAS...     

质子致DNA链断裂损伤的剂量效应研究

质子作为一种高传能线密度（LET）的辐射，具有能量沉积与局部剂量远大于低LET辐射（如X射线、γ射线和电子束等）的特点，通过物质时有完全不同的径迹结构，能够更有效的诱发DNA发生双链断裂，产生更多的不能修复性损伤，引起细胞的转化和死亡以及癌的发生等较高的相对生物效应（RBE）。在DNA分子水平上研究质子致生物损伤的机理，深入了解其辐射特点及危害程度，并研究相应的防护途径十分重要，     

不同LET碳离子对V79细胞辐射敏感性的影响

以中国仓鼠肺V79细胞为材料,利用兰州近代物理研究所重离子研究装置（HIRFL）产生的碳离子,研究了不同线性能量传递（LET）的重离子对体外培养细胞的存活效应,并与γ射线的结果作了比较。结果表明,不同LET碳离子引起细胞失活效应由大到小的顺序依次为125、200、700keV/μm。碳离子表现为无肩区的存活曲线,属单靶单击模型,γ射线表现为有肩区的存活曲线,属多靶单击模型。LET值为125、200、700keV/μm时得到的失活截面分别为35、12、8μm^2。当细胞存活比率为0.1和0.37,在LET为125keV/μm时得到相对生物学效应（RBE）值为1.47和2.19。     

空间环境和质子对水稻的诱变效应

利用返回式卫星搭载5个水稻品种的干种子进行空间诱变处理,以及用不同能量、剂量的质子辐射水稻干种子,研究其诱变效应。结果表明,空间环境对根尖细胞染色体有一定的致畸作用,能促进根尖细胞的有丝分裂活动,空间飞行中的水稻染色体畸变细胞率极显著高于地面对照组。与γ射线和质子处理比较,空间环境对染色体的致畸效应较低,而有丝分裂指数极显著高于质子和γ射线处理。空间环境对水稻M_1代幼苗的损伤效应亦低于质子和γ射线。空间环境和质子在M_2代能诱发较高频率的叶绿素缺失、株高和抽穗期突变,其有益性状突变的频率高于γ辐照的。     

纳秒级强脉冲电子束与Ar~＋离子束辐照作物种子后自由基产额的变化

应用多极板放电室产生的纳秒级强脉冲电子束与Ａｒ~＋离子束辐照蕃茄、黄瓜、辣椒和小麦的种子，分别测定辐照种子中的自由基产额，统计胚根根尖细胞中的染色体畸变频率和种子的萌发能力，藉以比较两种不同脉冲处理的辐照效果。实验发现：辐照处理时间的长短与自由基产额、染色体畸变率以及种子的萌发能力密切相关。辐照处理时间长，自由基产额高，染色体畸变率高，萌发生长能力低。四种作物种子的重复实验证明，电子脉冲的辐射效应明显强于Ａｒ~＋离子脉冲。     

~(60)Coγ射线诱发早熟凝聚染色体畸变的剂量效应关系

早熟染色体凝聚技术利用早熟染色体断片和环的数量衡量电离辐射诱发的染色体损伤程度。本实验结果表明,每个融合细胞中的染色体断片值随辐射剂量的增加而增加,畸变与剂量间可拟合为一定的数学模式。在各个剂量点上,早熟染色体断片产额明显高于常规染色体方法所检出的染色体畸变率,显示早熟染色体凝聚技术具有更高的辐射敏感性。     

18.8MeV质子与~(60)Coγ射线诱发人淋巴细胞染色体畸变比较

采用18.8 MeV单能质子和60Co γ射线对2名健康男性外周血进行照射,照射剂量分别为0.0、0.5、1.0、2.0、3.0、4.0和5.0 Gy,剂量率为0.5 Gy/min,观察染色体dic+r畸变,分别建立每细胞dic+r畸变率与18.8 MeV单能质子和60Coγ射线的剂量-效应曲线,并对生物效能进行比较.结果表明:18.8 MeV单能质子诱发人外周血淋巴细胞染色体dic+r畸变的最佳回归方程为Y=0.277?D?+0.013?D?2(r2=0.984,p<0.01),60Co γ射线为Y=0.035D+0.039D2(r2=0.991,p<0.01);质子诱发染色体畸变的RBE值的范围是0.91～1.87,质子照射在剂量较低时,有较高的生物效能;质子均匀照射诱发的染色体畸变dic+r在细胞间的分布符合泊松分布,与γ射线一致.     

氚诱发人淋巴细胞染色体畸变

本文介绍了用氚照射处于不同细胞周期的离体淋巴细胞所诱发的染色体畸变的剂量-效应关系。实验表明:~3H-TdR 或 HTO 照射 S 期,G_2期淋巴细胞诱发染色体单体型畸变;染色单体断裂与剂量呈线性关系,但~3H-TdR 每拉德诱发的每个细胞中的染色单体断裂产额约是 HTO 的10倍。HTO 照射 Go 期淋巴细胞诱发染色体型畸变。HTO 诱发双着丝点体加着丝点环与剂量的关系,适宜以 Y=αD βD_2表示。以~(60)Co-γ射线为参考辐射,HTO 诱发人淋巴细胞双着丝点体加着丝点环的 RBE 值,在本实验用的剂量率和剂量范围内不是恒定的,而是随β射线剂量的增加而降低,其波动范围在2.6—1.4之间。     

低能光子致DNA链断裂的蒙特卡罗模拟研究

为研究不同类型和能量的粒子照射细胞核DNA时导致的DNA损伤等辐射生物效应,建立了DNA、染色质原子模型,并开发了纳剂量蒙特卡罗程序NASIC。该程序可模拟包括光子、电子、质子在内的多种粒子在生物介质中的作用过程,既包括物理和化学径迹结构,也包括后续的生物响应过程。使用NASIC程序模拟了~(137)Cs源、Al的K层特征X射线(Al_K)源照射哺乳动物细胞后造成的单链断裂和双链断裂产额。研究结果表明,本文使用的DNA原子模型更加接近真实结构,DNA双链断链产额计算结果与实验值吻合较好。     

Modelling of Cellular Survival Following Chromosome Aberration

In order to assess the biological effectiveness of protons and heavy ions, a mechanistic model of cellular survival following radiation-induced chromosome aberrations was proposed. DNA damage repair module of nanodosimetry biophysical Monte Carlo simulation code (NASIC) was developed to simulate chromosome aberrations in nucleus induced by different types of particles at different linear densities of energy transfer (LET). Based on the analysis of radiation-induced chromosome aberration, a mechanistic model of cellular survival following radiation-induced chromosome aberrations was proposed. The parameters of the model could be obtained by fitting the experimental data of cell survival curves. For V79 cells exposed to X-rays and protons at different LET, the cell survivals calculated with the proposed model are in good agreement with the experimental data, and the correlation coefficient is 0.985 3. The proposed model was validated by experimental data of V79 cells exposed to ⁴He ions and the correlation coefficient of the cell survival calculated with the proposed model, and the experimental data is 0.931 1. The results show that the proposed model can distinguish the difference of cell survival for cells exposed to different types of particles at different LET.     

Killing effect of Chinese hamster V79 cells exposed to accelerated carbon ions and RBE determination

Survival curves of Chinese hamster V79 cells exposed to accelerated carbon ions with linear energy transfers of 125.5, 200 and 700keV/μm were measured, respectively. Inactivation cross sections corresponding to the irradiation above were deduced from the V79 cell survival curves. They are 7.86±0.17, 10.44±1.11 and 32.32±3.58μm2 in turn. With the surviving response of V79 cells to 60Co γ-rays as a reference value, relative biological effectiveness at 10%, 20%, 50% and 80% survival levels were given for the accelerated carbon ions. The results showed that carbon ions with LET of 125.5keV/μm had a higher value of RBE at all the four survival levels than the carbon ions with other LETs. It was prompted that the maximum value of RBE for the V79 cell surviving as the biological endpoint emerged at the LET below 200 keV/μm for carbon ions.     

中能碳离子束对不同贯穿深度上黑色素瘤B16细胞的辐照存活效应

测量了49．30MeV/u及经脊形过滤器展宽的Bragg峰的74.55MeV/u^12C离子束在不同贯穿深度上辐射后黑色素瘤B16细胞的存活率。结果显示,在以存活为终点的B16细胞生物学效应与碳离子束能量沉积同步增大。即Bragg或展宽的Bragg峰区内细胞存活率远低于离子束入射或出射通道处的细胞存活率。通过实验测量与剂量平均LET结合的线性平方模型理论计算存活曲线的比较,发现在实验测量误差范围内两者符合较好。提示：剂量平均LET结合线性平方模型可能是预测中能重离子束贯穿深度上B16细胞存活效应的一种有效的方法。     

重离子束诱发细胞染色体断裂产额的计算模拟

建立了一种简捷的方法来计算细胞接受重离子照射后发生染色体断裂的产额。L02细胞接受碳离子照射后染色体断裂的产额,并应用早熟染色体凝集技术获得该细胞在经重离子照射后的染色体断裂产额的实验值。通过理论计算,得到了^12C^6＋照射人正常肝细胞L02后不同吸收剂量点的染色体断裂产额,与应用早熟染色体凝集技术实验中实际获得的染色体断裂产额基本吻合。说明,细胞在接受重离子束照射的初始阶段可能是物质相互作用的物理过程,细胞内的生物机能对这一过程的干预尚未启动。提示重离子的高相对生物学效应与重离子的物理特性密切相关。     

Bystander effect in human hepatoma HepG2 cells caused by medium transfers at different times after high-LET carbon ion irradiation

Although radiation-induced bystander effects have been well documented in a variety of biological systems, whether irradiated cells have the ability to generate bystander signaling persistently is still unclear and the clinical relevance of bystander effects in radiotherapy remains to be elucidated. This study examines tumor cellular bystander response to autologous medium from cell culture irradiated with high-linear energy transfer (LET) heavy ions at a therapeutically relevant dose in terms of clonogenic cell survival. In vitro experiments were performed using human hepatoma HepG2 cell line exposed to 100 keV/μm carbon ions at a dose of 2 Gy. Two different periods (2 and 12 h) after irradiation, irradiated cell conditioned medium (ICCM) and replenished fresh medium were harvested and then transferred to unirradiated bystander cells. Cellular bystander responses were measured with the different medium transfer protocols. Significant higher survival fractions of unirradiated cells receiving the media from the irradiated cultures at the different times post-irradiation than those of the control were observed. Even replenishing fresh medium for unirradiated cells which had been exposed to the ICCM for 12 h could not prevent the bystander cells from the increased survival fraction. These results suggest that the irradiated cells could release unidentified signal factor(s), which induced the increase in survival fraction for the unirradiated bystander cells, into the media sustainedly and the carbon ions triggered a cascade of signaling events in the irradiated cells rather than secreting the soluble signal factor(s) just at a short period after irradiation. Based on the observations in this study, the importance of bystander effect in clinical radiotherapy was discussed and incorporating the bystander effect into the current radiobiological models, which are applicable to heavy ion radiotherapy, is needed urgently.     

Evaluation of radiosensitivity of human tumor cells after irradiation of γ-rays based on G2-chromosome aberrations

The aim of the present investigation is to determine initial G2-chromosome aberrations and to validate whether the G2-chromosome aberrations can predict the cellular clonogenic survival in human tumor cell lines. Cell lines of human ovary carcinoma cells (HO8910) and human hepatoma cells (HepG2) were irradiated with a range of doses and assessed both for initial G2-chromosome aberrations and for cell survival after γ-irradiation. The initial G2-chromosome aberrations were measured by counting the number of G2-chromatid breaks after irradiation, detected by the premature chromosome condensation technique, and the G2-assay method. Cell survival was documented by a colony formation assay. A linear-quadratic survival curve was observed in both cell lines. The dose-response results show that the numbers of G2-chromatid breaks increase with the increase in dose in the two cell lines. At higher doses (higher than 4 Gy) of irradiation, the number of G2-chromatid breaks for the G2-assay method cannot be determined because too few cells reach mitosis, and hence their detection is difficult. A good correlation is found between the clonogenic survival and the radiation-induced initial G2-chromatid breaks per cell (r=0.9616). The present results suggest that the premature chromosome condensation technique may be useful for determining chromatid breaks in G2 cells, and the number of initial G2-chromatid breaks holds promise for predicting the radiosensitivity of tumor cells.     

Evaluation of radiosensitivity of human tumor cells after irradiation of γ-rays based on G2-chromosome aberrations

1 Introduction It is well established that the radiosensitivity is dependent on cell-cycle progression, and among stages of interphase, G2 phase is the most radiosensitive fol- lowed by G1 phase, and S phase, which is the least ra- diosensitive, whereas G0 phase is radioresistant under conditions of oxygen deprivation and sufficient repair time [1-3]. Previous studies have concluded that the G2 phase is a very important stage. Some researchers have studied the chromosome aberrations in G2 ph…     

质子核反应二次粒子引起的静态存储器单粒子翻转截面计算

研究建立了质子单粒子翻转截面计算方法。基于蒙特卡罗软件Geant4,计算分析了不同能量质子核反应产生二次粒子对有效体积带来的影响,确定了有效体积大小。计算了静态随机存取存储器的质子单粒子翻转截面和多位翻转截面。计算结果在趋势上与双参数公式所预言的相符合,并可得到很高能量质子引起的极限截面;在较低能段的数据与文献的理论和实验值相符。