不同LET射线对细胞的生物学效应

以人肝癌细胞系和正常肝细胞系为材料,报道了不同传能线密度射线辐射引发细胞染色体原初断裂及24h内的修复情况。计算了相对生物学效应的值。以L02染色体总断裂数量得出的RBE值96.05keV/μm的12C6+为3.6,512keV/μm36Ar18+为2.9。而以7721染色体总断裂数量得出的RBE值:96.05keV/μm的12C6+为3.5,512keV/μm36Ar18+也为2.9。用产生等点染色单体断裂计算,则RBE更高。对比得出,高LET对增加等点染色单体断裂量的作用要远远大于对增加染色单体断裂量的作用。等点染色单体的断裂修复难度要远远大于染色单体断裂的修复难度,这也是高LET高致死率的一个重要原因。

Survivin表达对HepG2细胞高LET射线辐射敏感性的影响

<正>Survivin是1997年发现的凋亡抑制蛋白家族(IAPs)的成员,它特异性的表达于大多数的恶性肿瘤细胞中,而在正常组织中检测不到,具有组织特异性。以前的研究表

不同LET ~(12)C~(6+)离子对生防菌BJ1的辐射诱变效应

选取高低两个LET点(40和60keV/m),剂量点分别为50,100,200,400,600Gy进行辐照处理,研究了生防菌的存活率与突变率的关系,抑菌谱以及活性等。结果表明,在高LET条件下,低剂量辐照就可以得到较多的突变体,并且BJ1有较高的存活率和突变谱,有利于筛选优良的正突变体。因此高LET较低LET有更为明显的辐射诱变效应。

高LET重离子照射人肿瘤细胞的DNA双链断裂及修复研究

依托兰州近代物理研究所的HIRFL装置对人肝癌细胞SMMC-7721进行高LET的重离子辐照,同时利用脉冲场凝胶电泳研究高LET辐射引起的细胞DSB及其修复的特点。对于不同离子的辐射进行了比较分析,探索重离子的辐射生物学效应机理。结果发现,随着剂量的增加,初始DSB在给定剂量范围内呈线性增长,LET较高的氩离子的剂量效应曲线具有较大的斜率。对于DSB分布情况的研究发现,LET不同,大小片段的分布随着剂量的变化呈现不同的变化情况。修复研究显示两种LET辐射的快修复在30min左右都已经结束,此后都开始了慢修复,对于高LET的氩离子辐射来说,快修复和慢修复完成的修复量均高于较低LET的碳离子辐射。4h时,两种辐射残余的DSB基本一致。结果证明了高LET辐射下初始DSB与剂量的线性依赖关系,且发现不同种类的离子辐射引起的DSB的剂量效应曲线的斜率不同。结果也显示了DSB的非随机分布现象和DSB修复的双阶段模式,发现LET、离子种类和剂量对于DSB的片段非随机分布同时存在影响,同时修复结果提示慢修复机制和错修复在高LET辐射引起损伤的修复研究中可能具有重要意义。

不同LET辐射对HepG2肝癌细胞的辐射敏感性与周期阻滞的影响

本工作研究不同LET射线辐照对HepG2肝癌细胞辐射敏感性、周期进程和凋亡的影响,为重离子治疗癌症的临床应用积累基础数据。以0、0.5、1、2、4、8Gy剂量的12C6+离子及X射线分别照射处于指数生长期的HepG2细胞,用克隆形成率测定细胞辐射敏感性,通过流式细胞术测定细胞DNA含量以确定各时相细胞的比例及细胞凋亡情况。实验结果显示,12C6+离子辐照所致的HepG2细胞存活率明显低于X射线。随着吸收剂量的增加和修复时间的延长,12C6+离子能导致更显著的细胞S期阻滞、G2/M期阻滞延迟和细胞凋亡。说明与X射线相比,12C6+离子辐照能更有效地杀伤HepG2肝癌细胞并诱导其凋亡。

G2期早熟染色体凝集技术预测肝癌细胞低LET射线辐射敏感性

用60Co产生的γ射线照射人肝癌细胞系SMMC-7721。以克隆形成法测定经照射后的细胞存活率,用化学诱导剂Calyculin-A诱导的早熟染色体凝集(Prematurechromosomecondensation,PCC)技术研究染色体损伤。结果显示G2期细胞内的染色单体和等点染色单体断裂数与照射剂量之间存在着线性相关性,染色单体断裂数与细胞存活率之间存在较好的线性相关性。表明辐射诱导的染色单体断裂可以作为预测SMMC-7721细胞内在辐射敏感性的指标,也可为临床诊断和治疗肝癌提供依据。

G2期早熟染色体凝集技术预测肝癌细胞低LET射线辐射敏感性(英文)

　应用60Co产生的γ射线照射人肝癌细胞系SMMC-7721,以克隆形成法测定经照射后的细胞存活率,用化学诱导剂Calyculin-A.诱导的早熟染色体凝集技术研究染色体损伤.结果显示G2期细胞内的染色单体和等点染色单体断裂数与照射剂量之间存在着线性相关性,染色单体断裂数与细胞存活率之间存在较好的线性相关性.表明辐射诱导的染色单体断裂可以作为预测SMMC-7721细胞内在辐射敏感性的指标,也可为临床诊断和治疗肝癌提供依据.

利用HIRFL加速的重离子获得半导体器件的σ-LET曲线

表征器件单粒子敏感度的σ-LET 曲线是轨道翻转率预估的重要依据.利用兰州重离子加速器（HIRFL）加速的 35 MeV/u的36Ar离子和 15.14 MeV/u的136Xe离子得到的 32 kbit×8静态存储器（SRAM）IDT71256单粒子翻转的实验数据,用Weibull和Lognormal两种函数拟合获得了完整的σ-LET 曲线,对两种拟合结果的差别进行了讨论,并在拟合参数的基础上估算了地球同步轨道和两条太阳同步轨道辐射环境中IDT71256的翻转率.

不同LET的重离子辐射对DSB诱导的影响

利用γ射线和不同LET的碳离子辐照小鼠B16黑色素瘤细胞的脱蛋白DNA ,采用脉冲场凝胶电泳结合荧光扫描技术研究了DNA双链断裂 (DSB)与LET之间的关系。结果表明 :不同LET重离子诱导的PR都随剂量的增加而增加 ,并在超过一定的剂量之后逐渐趋于一个准阈值 :而不同LET的重离子诱导的L值都与剂量呈线性关系 ;对于诱导DSB的RBE值则随着LET的增加先呈上升趋势 ,在LET超过 10 0ke μm后下降。

不同LET碳离子对哺乳动物细胞的生物学效应

目的　研究不同传能线密度 (LET)的重离子对体外培养细胞存活率、微核率和染色体畸变的效应。方法　用集落形成法研究细胞的存活情况 ,观察统计细胞微核率和染色体结构的变化。结果　①细胞存活 :不同LET碳离子引起细胞失活效应由大到小的顺序依次为 12 5 ,2 0 0 ,70 0keV μm。②细胞微核 :相同剂量下 ,2 0 0keV μm碳离子所致微核率高于 70 0keV μm时的结果。③染色体畸变 :可看到多种染色体结构变异。结论　在本实验中 ,LET为 12 5keV μm的碳离子引起的失活效应最大 ,2 0 0keV μm碳离子引起的微核率高于 70 0keV μm碳离子引起的微核率

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 12 5、2 0 0、70 0keV/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 12 5、2 0 0、70 0keV/μm时得到的失活截面分别为 35、12、8μm2 。当细胞存活比率为 0 .1和 0 .37,在LET为 12 5keV/μm时得到相对生物学效应 (RBE)值为1.4 7和 2 .19。

Survivin expressions in human hepatoma HepG2 cells exposed to ionizing radiation of different LET

Survivin is a member of the inhibitors of apoptosis (IAP) protein family that interferes with post-mitochondrial events including activation of caspases. To examine the regulation of survivin expression in response to irradiation with different linear energy transfer (LET), human hepatoma HepG2 cells were irradiated in vitro with X-rays and carbon ions. Cellular sensitivities to low- and high-LET radiation were determined by colony formation. Survivin expression at mRNA and protein level were measured with RT-PCR and Western blot analyses, respectively. Radiation-induced cell cycle arrest and apoptosis were investigated with flow cytometry. We found that low-LET X-rays induced dose-dependent increases in survivin expression. After exposure to high-LET carbon ions, survivin expression gradually increased from 0 to 4 Gy, and then declined at 6 Gy. More pronounced survivin expression, stronger G(2)/M phase arrest was observed after exposure to carbon ions in comparison with X-rays at doses from 0 to 4 Gy. These observations indicate that there is a differential survivin expression in response to different LET radiations and the cycle arrest mechanism may be associated with it. In addition, our data on induction of apoptosis are compatible with the assumption that survivin expression induced by low-LET X-rays radiation may play a critical role in inhibiting apoptosis. However, after irradiation with ions, an anti-apoptotic function of survivin is not evident, possibly because of the serious damage produced by densely ionizing radiation.

Biodosimetry estimate for high-LET irradiation

The purpose of this paper is to prepare for an easy and reliable biodosimeter protocol for radiation accidents involving high-linear energy transfer (LET) exposure. Human peripheral blood lymphocytes were irradiated using carbon ions (LET: 34.6 keV mu m(-1)), and the chromosome aberrations induced were analyzed using both a conventional colcemid block method and a calyculin A induced premature chromosome condensation (PCC) method. At a lower dose range (0-4 Gy), the measured dicentric (dics) and centric ring chromosomes (cRings) provided reasonable dose information. At higher doses (8 Gy), however, the frequency of dics and cRings was not suitable for dose estimation. Instead, we found that the number of Giemsa-stained drug-induced G2 prematurely condensed chromosomes (G2-PCC) can be used for dose estimation, since the total chromosome number (including fragments) was linearly correlated with radiation dose (r = 0.99). The ratio of the longest and the shortest chromosome length of the drug-induced G2-PCCs increased with radiation dose in a linear-quadratic manner (r = 0.96), which indicates that this ratio can also be used to estimate radiation doses. Obviously, it is easier to establish the dose response curve using the PCC technique than using the conventional metaphase chromosome method. It is assumed that combining the ratio of the longest and the shortest chromosome length with analysis of the total chromosome number might be a valuable tool for rapid and precise dose estimation for victims of radiation accidents.

Protective effects of melatonin against low- and high-LET irradiation

To investigate the protective effects of melatonin against high-LET ionizing radiation, V79 Chinese hamster cells were irradiated with 100 keV/mu m carbon beam. Parallel experiments were performed with 200 kV X-rays. To avoid the impact from extra solvents, melatonin was dissolved directly in culture medium. Cells were cultured in melatonin medium for 1 hr before irradiation. Cell inactivation was measured with conventional colony forming assay, medium containing 6-thioguanine was used for the selection of mutants at hprt locus, and the cell cycle was monitored by flow cytometry. Both carbon beam and X-rays induced cell inactivation, hprt gene mutation and cell cycle G2 block dose-dependently. But carbon beam showed stronger effects as indicated by all three endpoints and the relative biological effectiveness (RBE) was 3.5 for cell killing (at 10% survival level) and 2.9 for mutation induction (at 5 x 10(-5) mutants/ cell level). Melatonin showed protective effects against ionizing radiation in a dose-dependent manner. In terms of cell killing, melatonin only increased the survival level of those samples exposed to 8Gy or larger of X-rays or 6 Gy or larger of carbon beam. In the induction of hprt mutation and G2 block, melatonin reduced such effects induced by carbon beam but not by X-rays. The results suggest that melatonin reduces the direct interaction of particles with cells rather than an indirect interaction. Further studies are required to disclose the underlying mechanisms.