放射性离子束~9C的细胞生物学效应

首先介绍了重离子束治癌的特点及当前的技术进步, 着重讨论了放射性离子束(RIB)在肿瘤治疗上增添的优势, 详细叙述了在日本放射医学综合研究所(NIRS)重离子医用加速器(HIMAC)上旨在肿瘤治疗的放射性离子束 C 的实验研究, 包括束流产生、参数优化、深度物理剂量分布、细胞辐照后的存 9活效应以及 C 和 C 束的相对生物效率(RBE)比较. 最终结果: 在40 mm 厚铍靶、10 mm 厚铝降能器、 9 125%动量接收度时, 采用 430 MeV/u、1.8×109 粒子/s 的初试束 C, 得到的 C 束的产生率为 9.07×10?6, 12 9纯度为 82.88%, 采用点扫描技术时, 在直径为 10 mm 的中心面积内, 可获得均匀度为 89.6%的辐照场,这时在入口处的剂量率为0.5Gy/h. 在Bragg峰附近范围内的细胞存活实验中, C束的平均RBE为5.28, 9而 C 束的平均 RBE 为 2.93, C 束的 RBE 要比 C 束的高1.8 倍, 这显示 C 束在 Bragg 峰附近范围内, 12 9 12 9对细胞的杀伤力要比 C 强, 在肿瘤治疗上会更有效. 12

重离子束生物工程中的一些基本物理问题

本文介绍了重离子束的基本特性和在生命科学应用中的优势,以及它的能区划分,传能线密度LET,相对生物效率RBE等,分别叙述了中、高能和低能离子束与介质作用的特点、在农学中应用的模式及其吸收剂量的计算,最后还对一些机理问题进行了简单讨论。

重离子~(12)C对~(60)Coγ射线诱发人染色体畸变效应的比较研究

目的　重离子和高剂量率6 0 Coγ射线照射离体人血建立染色体畸变的剂量 效应曲线 ;比较重离子1 2 C照射与6 0 Coγ射线照射诱发染色体畸变的相对生物效能。方法　重离子1 2 C和6 0 Coγ射线照射离体人血 ,吸收剂量率为 3Gy min ,吸收剂量为 1 0～ 8 0Gy。主要记录染色体型畸变的非稳定性畸变 ,对双着丝粒体和着丝粒环做曲线拟合 ,并检验回归系数的显著性和曲线的拟合度。结果　重离子1 2 C和6 0 Coγ射线照射离体血诱发的染色体畸变 (双 +环 ) ,在 0～ 8Gy范围内 ,呈良好的剂量 效应关系。1 2 C离子诱发染色体畸变的RBE值是不恒定的 ,它随吸收剂量增加而减少 ,在 0 3～ 8 0Gy范围内 ,RBE值 (Dγ Dc)从 2 6 2到 1 0 0 ,平均 1 5 8。结论　1 2 C离子对6 0 Coγ射线照射诱发染色体畸变 ,在照射剂量较低时 ,有较高的生物效应。

碳离子辐照细胞的相对生物学效率

研究了传能线密度 (LET)≥ 1 2 5.5keV μm的碳离子辐照小鼠黑色素瘤B1 6、人的宫颈癌HeLa、中国仓鼠肺V79、人的肝癌SMMC 772 1 4种细胞的相对生物学效率 (RBE) .得到了当LET =1 2 5.5keV μm时 ,RBE依赖于细胞种类并随细胞存活水平的升高而增加的关系 ,以及当LET≥ 1 2 5.5keV μm时 ,RBE随着LET的增大而变小的关系

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。

重离子束在医学治疗中的应用

重离子束治癌是重离子束在医疗领域中的一项典型的应用技术 .文章从重离子束在物理学与生物学上的特点 ,描述了它对肿瘤治疗具有的优越性 :物理剂量深度分布在射程末端有一个能量沉积集中区 ,其深度和大小均可调节 ;在靶区的相对生物效率 (RBE)高、氧增比 (OER)低 ;射程歧离与横向散射小 ;利用正电子发射断层照相 (PET)技术可以实时在线监测 ;可以三维扫描进行适形治疗 ;半致死损伤修复小 ;辐射敏感性不依赖细胞周期时相 .文章还介绍了这项技术的国内外进展 ,并对其未来进行了展望 .

三种瘤细胞对重离子和γ射线的辐射敏感性

目的　比较体外培养的瘤细胞对重离子和γ射线的辐射敏感性。方法　以人肝癌SMMC 772 1、宫颈癌HeLa和小鼠黑色素瘤B16细胞为材料 ,用集落形成法研究了细胞经γ射线和重离子处理后的存活情况。结果　细胞经γ射线处理后均表现为有肩区的存活曲线 ,属多靶击中模型。细胞经重离子处理后表现为无肩区的存活曲线 ,属单靶击中模型 ,在细胞存活分数为 5 0 %和 10 %时得到SMMC 772 1、HeLa、B16细胞的RBE值分别为 3 40、2 76、4 6 7和 1 88、1 5 3、2 2 2。结论　在相同剂量下 ,重离子能更有效地杀灭瘤细胞

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。

仓鼠V79细胞对加速碳离子的辐照致死效应

分别测定了传能线密度（LET）为125．5、200、700keV／μm碳离子辐照仓鼠V79细胞的存活曲线，由存活曲线确定了上述3种碳离子辐照时V79细胞的失活截面依次为7．86±0．17、10．44±1．11、32．32±3．58μm2。以V79细胞对60Coγ射线的存活响应为参考值，给出了对应于上述3种碳离子照射周％、20％、50％、80％存活水平下的相对生物学效应（RBE），结果表明125．5keV／μm碳离子的RBE值在各个存活水平下都为最大。提示：以存活为生物学终点的RBE最大值在LET值小于200keV／μm的碳离子辐照时出现。

Radiosensitivity of hepatoma cell lines and human normal liver cell lines exposed in vitro to carbon ions and argon ions at the HIRFL

Human hepatoma (SMMC-7721) and normal liver (L02) cells were irradiated with c-rays, 12C6+ and 36Ar18+ ion beams at the Heavy Ion Research Facility in Lanzhou (HIRFL). By using the Calyculin-A induced premature chromosome condensation technique, chromatid-type breaks and isochromatid-type breaks were scored separately. Tumor cells irradiated with heavy ions produced a majority of isochromatid break, while chromatid breaks were dominant when cells were exposed to c-rays. The relative biological effectiveness (RBE) for irradiation-induced chromatid breaks were 3.6 for L02 and 3.5 for SMMC-7721 cell lines at the LET peak of 96 keVlm 1 12C6+ ions, and 2.9 for both of the two cell lines of 512 keVlm 1 36Ar18+ ions. It suggested that the RBE of isochromatid-type breaks was pretty high when high-LET radiations were induced. Thus we concluded that the high production of isochromatid-type breaks, induced by the densely ionizing track structure, could be regarded as a signature of high-LET radiation exposure.

~(12)C~(6+)重离子束照射治疗复发性软组织肉瘤临床疗效探讨

目的: 应用我国自主研发的重离子加速器产生的12C6+重离子束治疗复发性软组织肉瘤,评价其高线性能量传递 (LET)及低 LET在临床应用中的优劣. 方法: 3例经病理证实为软组织肉瘤自愿接受重离子束照射的患者,其中 2例病变位于腹部,1例在背部. 所有患者均为手术复发 2次以上,最多达 6次,并经手术行常规放疗失败. 应用 80～100mev/u重离子束对 3例患者分别给予总剂量 72～120 GyE/6212 f照射,生物效应剂量 (RBE) =3. 结果:2例患者 3mo后病变完全消失,达临床治愈;1例缩小 75%,达临床部分缓解,总有效率为100%.治疗中及治疗后照射野皮肤无破溃等放射性损伤.结论:12C6+重离子束具有治疗精度高,疗程短,对肿瘤周围正常组织损伤小等特点. 特别在射线抗拒的难治性肿瘤中可达到常规放疗难以实现的疗效,具有很好的临床应用前景.

Linear energy transfer dependence of the effects of carbon ion beams on adventitious shoot regeneration from in vitro leaf explants of Saintpaulia ionahta

Purpose: To determine the effects of carbon ion beams with five different linear energy transfer (LET) values on adventitious shoots from in vitro leaf explants of Saintpaulia ionahta Mauve cultivar with regard to tissue increase, shoots differentiation and morphology changes in the shoots. Materials and methods: In vitro leaf explant samples were irradiated with carbon ion beams with LET values in the range of 31 similar to 151 keV/mu m or 8 MeV of X-rays (LET 0.2 keV/mu m) at different doses. Fresh weight increase, surviving fraction and percentage of the explants with regenerated malformed shoots in all the irradiated leaf explants were statistically analysed. Results: The fresh weight increase (FWI) and surviving fraction (SF) decreased dramatically with increasing LET at the same doses. In addition, malformed shoots, including curliness, carnification, nicks and chlorophyll deficiency, occurred in both carbon ion beam and X-ray irradiations. The induction frequency with the former, however, was far more than that with the X-rays. Conclusions: This work demonstrated the LET dependence of the relative biological effectiveness (RBE) of tissue culture of Saintpaulia ionahta according to 50% FWI and 50% SF. After irradiating leaf explants with 5 Gy of a 221 MeV carbon ion beam having a LET value of 96 keV/mu m throughout the sample, a chlorophyll-deficient (CD) mutant, which could transmit the character of chlorophyll deficiency to its progeny through three continuous tissue culture cycles, and plantlets with other malformations were obtained.

Chromosomal aberrations induced by C-12(6+) ions and Co-60 gamma-rays in mouse immature oocytes

The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of C-12(6+) ion or Co-60 gamma-ray. Chromosomal aberrations were analyzed in metaphase II oocytes at 7 weeks after irradiation. The relative biological effectiveness (RBE) of C C-12(6+) ion was calculated with respect to Co-60 gamma-ray for the induction of chromosornal aberrations. The C-12(6+) ion and Co-60 gamma-ray dose-response relationships for chromosomal aberrations were plotted by linear quadratic models. The data showed that there was a dose-related increase in frequency of chromosomal aberrations in all the treated groups compared to controls. The RBE values for C-12(6+) ions relative to (CO)-C-60 gamma-rays were 2.49, 2.29, 1.57, 1.42 or 1.32 for the doses of 0.5, 1.0, 2.07 4.0 or 6.0 Gy, respectively. Moreover, a different distribution of the various types of aberrations has been found for C-12(6+) ion and Co-60 gamma-ray irradiations. The dose-response relationships for C-12(6+) ion and (CO)-C-60 gamma-ray exhibited positive correlations. The results from the present study may be helpful for assessing genetic damage following exposure of immature oocytes to ionizing radiation.

The influence of fractionation on cell survival and premature differentiation after carbon ion irradiation

Carbon ion radiotherapy/Fractionated irradiation/R-BE/Premature terminal differentiation. To investigate the influence of fractionation on cell survival and radiation induced premature differentiation as markers for early and late effects after X-rays and carbon irradiation. Normal human fibroblasts NHDF, AG1522B and WI-38 were irradiated With 250 kV X-rays, or 266 MeV/u, 195 MeV/u and I I MeV/u carbon ions. Cytotoxicity was measured by a clonogenic survival assay or by determination of the differentiation pattern. Experiments with high-energy carbon ions show that fractionation induced repair effects are similar to photon irradiation. The RBE10 values for clonogenic survival are 1.3 and 1.6 for irradiation in one or two fractions for NHDF cells and around 1.2 for AG1522B cells regardless of the fractionation scheme. The RBE for a doubling of post mitotic fibroblasts (PMF) in the population is I for both single and two fractionated irradiation of NHDF cells. Using I I MeV/u carbon ions, no repair effect can be seen in WI-38 cells. The RBE10 for clonogenic survival is 3.2 for single irradiation and 4.9 for two fractionated irradiations. The RBE for a doubling of PMF is 3.1 and 5.0 for single and two fractionated irradiations, respectively. For both cell lines the effects of high-energy carbon ions representing the irradiation of the skin and the normal tissue in the entrance channel are similar to the effects of X-rays. The fractionation effects are maintained. For the lower energy, which is representative for the irradiation of the tumor region. RBE is enhanced for clonogenic survival as well as for premature terminal differentiation. Fractionation effects are not detectable. Consequently, the therapeutic ratio is significantly enhanced by fractionated irradiation with carbon ions.

The experimental measurement of the relative biological effectiveness of carbon ions with different qualities

The relative biological effectiveness (RBE) of carbon ions with linear energy transfer (LET) of 172 keV/mu m and 13.7 keV/mu m were determined in this study. The clonogenic survival and premature terminal differentiation were measured on normal human. broblasts AG01522C and NHDF after exposure of the cells to 250 kV X-rays and carbon ions with different qualities. RBE was determined for these two biological end points. The results showed that the measured RBE10 with a survival fraction of 10% was 3.2 for LET 172 keV/mu m, and 1.33 for LET 13.7 keV/mu m carbon ions. RBE for a doubling of post-mitotic. broblasts (PMF) in the population was 2.8 for LET 172 keV/mu m, and 1 for LET 13.7 keV/mu m carbon ions. For the carbon ion therapy, a high RBE value on the Bragg peak results in a high biological dose on the tumour. The tumour cells can be killed effectively. At the same time, the dose on healthy tissue would be reduced accordingly. This will lighten the late effect such as fibrosis on normal tissue.