重离子12 C诱发人淋巴细胞染色体畸变和微核的研究

目的 探讨不同LET重离子12C诱发人淋巴细胞的生物效应.方法 采集2名健康男性自愿献血者血样,用60Co γ射线及LET为29和148 keV/μm的12C重离子照射,剂量为0.5～5.0 Gy,剂量率为0.5 Gy/min.采用同时加秋水仙素和松胞素B的方法,检测了淋巴细胞染色体畸变双着丝粒和着丝粒环(双加环)及淋巴细胞微核.结果 29和148 keV/μm的重离子12C诱导染色体畸变和微核的剂量-效应关系分别为线性和线性平方模式.诱发的染色体畸变率随着LET的增高而增高;诱发的微核率剂量＜3.0 Gy,随着LET的增高而增高,剂量＞3.0 Gy微核率趋于饱和.148 keV/μm的12C离子诱导的染色体畸变双加环,随着培养时间的延长,从0.41 ～ 1.32增加到0.68 ～ 3.00.结论 重离子12C诱导的染色体畸变随着时间和LET的增高而增加,微核在一定剂量范围内随着LET的增高而增加,其生物效应比低LET辐射60Co γ射线强.     

多色荧光原位杂交显带技术在高、低传能线密度辐射损伤中的应用

淋巴细胞染色体畸变率与电离辐射密切相关,并且已经广泛应用于辐射损伤的生物剂量评估.多色荧光原位杂交显带技术(mBAND)是染色体畸变检测的重要新兴技术,并且逐步应用于不同传能线密度(LET)射线所引起的染色体畸变检测.该文对mBAND技术在X、γ射线所属的低LET射线和太空射线及高能重离子流所属的高LET射线中的应用,二者引起不同染色体畸变类型以及产生的不同辐射生物剂量效能作综合阐述.     

高LET辐射导致大量非再结合的DNA断裂

电离辐射杀死哺乳动物细胞的机制,在分子水平上还未阐明,而具有高线性能量转移(LET)的辐射,对于研究这些机制可作为重要的工具。已经知道,每单位剂量的高 LET 辐射如中子、π介子和低能量重离子比电离散射(diffuse)或低 LET 如γ或X 射线(在体外)能更有效的杀死细菌、酵     

不同传能线密度射线0~1Gy照射诱发染色体畸变的量-效关系研究

目的 建立0~1Gy范围内⁶⁰Coγ射线、 ²⁵²Cf 中子、单能中子及 ¹²C 重离子诱发染色体畸变剂量-效应曲线,用于评价职业受照或低剂量辐射损伤。方法 采用不同照射装置1Gy以内照射离体人外周血,于培养开始加秋水仙素,培养48h收获,制备染色体标本,Metafer中期细胞自动寻找系统,人机交互计数染色体畸变,最优拟合数据得到相应模型。结果 在低剂量范围内,以双着丝粒体+环(dic+r)为终点,⁶⁰Coγ射线为线性模型, ²⁵²Cf 中子、单能中子及 ¹²C 重离子为线性平方模型;以无着丝粒断片(ace)为终点,⁶⁰Coγ射线和 ¹²C 重离子为线性平方模型, ²⁵²Cf 中子和单能中子为线性模型;以总畸变为终点,4种射线均为线性平方模型。结论 高传能线密度(LET)射线损伤效应高于低LET射线,4种射线损伤效应依次为 ²⁵²Cf 混合中子 >单能中子> ¹²C 重离子> ⁶⁰Co γ射线。在低剂量范围内dic+r指标适用于高LET照射的剂量估算。     

重离子12C6+对60Coγ射线诱发淋巴细胞微核效应的比较研究

目的 比较重离子束^12C^6 对^60Coγ射线照射人离体血诱发淋巴细胞微核的效应。方法 用^60Coγ射线和地面加速器产生的重离子^12C^6 (平均LET为36．70keV/μm)，不同剂量照射离体人血，用CB微核法观察双核淋巴细胞的微核，计算重离子束^12C^6 对^60Coγ射线的相对生物效能。结果 在0-6 Gy剂量范围内，重离子束^12C^6 对^60Coγ射线的相对生物效能在4．19～1．78之间，平均为2．56。结论 重离子束^12C^6 比^60Coγ射线有更高的生物效应。     

钚α射线辐照后染色体的不稳定性遗传

实验研究了稀疏型,低LET与密集型、高LET电离辐射对骨髓造血系统不同的生物学效应。将正常CBA/H雄性小鼠骨髓细胞用Goodhead(1991)研制的~(238)8puα射线辐射装置辐射,剂量分     

中子辐射损伤效应、机制及防护措施研究进展

随着各国对核武器研发力度的逐渐增强,以及中子在经济生产领域中应用的推广,中子辐射致伤事件时有发生。中子射线作为一种高传能线密度（LET）射线,具有伤亡率高、症状严重、愈后差的特点,故相比于低LET射线产生的损伤,其防护和治疗更加困难。本文主要介绍近年来中子辐射的效应、内在损伤机制和临床防护措施等方面的研究进展,为制订合理高效的防治方案提供理论指导。     

基于不同相对生物效应模型评估质子放疗生物剂量

目的:评估两种相对生物效应模型计算的生物剂量,并与传统临床质子放疗生物剂量相比较。方法:使用粒子模拟工具(TOPAS)分别在水箱和两例患者模体(脑部和前列腺)计算物理剂量、剂量平均LET (dose averaged linear energy transfer, LET d)和径迹平均LET (track...     

重离子12C对60Coγ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^60Coγ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^12C照射与^60Coγ射线照射诱发染色体畸变的相对生物效能。方法 重离子^12和^60Coγ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^12C和^60Coγ射线照射离体血诱发的染色体畸变(双 环)，在0—8Gy范围内，呈良好的剂量一效应关系。^12C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(Dr/Dc)从2．62到1．00，平均1．58。结论 ^12C离子对^60Coγ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。     

重离子辐射的细胞突变效应

重离子治癌作为一种新的疗法应用越来越广泛，同时，随着宇航事业的发展，有关重离子辐射的生物效应研究日益增多。本文对重离子辐射所致细胞的突变效应与其各种物理参数如粒子注量、突变截面的关系及重离子辐射致突变的相对生物效应和特点等作了扼要介绍     

重离子治疗恶性黑色素瘤的研究进展

恶性黑色素瘤是来源于黑色素细胞的一类恶性肿瘤,常见于皮肤,亦见于黏膜、眼脉络膜等部位。恶性黑色素瘤是皮肤癌中最具侵袭性的恶性肿瘤,转移早、死亡率高,且具有放射抗拒性,对常规射线不敏感。重离子束的应用为恶性黑色素瘤患者提供了一种更有效的治疗手段。重离子由于其特有的深度剂量分布,能使大部分吸收剂量沉积于肿瘤部位,从而有效地保护周围的健康组织,并且具有相对生物效应高、氧效应低等特点,是目前较好的放射治疗方法。现从重离子治疗恶性黑色素瘤的生物学效应以及临床应用的最新进展进行综述,为重离子应用于恶性黑色素瘤的临床治疗及推广提供参考。     

New modalities in cancer treatment: heavy charged particles

Heavy charged particles represent the ultimate that the physicist can contribute to the development of radiation sources for therapy. Of the heavy charged particles, protons are the least expensive to accelerate and can be manipulated to give a sharply defined high-dose volume with a rapid fall-off of dose outside the target area. The biological properties of protons do not differ significantly from X or gamma rays. Negative pi mesons require an elaborate accelerator for their production. Pions offer the possibility of concentrating energy, some of it densely ionizing with a reduced oxygen enhancement ratio and elevated biological effectiveness within the designated tumour volume, while minimizing the dose of sparsely ionizing radiation to the normal tissues traversed. High-energy heavy ions offer the greatest flexibility and allow localized dose distributions and also, with the higher Z particles, a substantial reduction of the oxygen enhancement ratio can be achieved. The ultimate choice of particle depends upon what turns out to be the most important factor in radiotherapy--an improved localization of dose or a reduction in the dependence of cell killing on the presence of molecular oxygen.     

Assessment of the homogeneous efficacy of carbon ions in the spread-out Bragg peak for human lung cancer cell lines

Purpose The aim of this study was to assess the radiosensitivities and homogeneous efficacy in the spread-out Bragg peak (SOBP) for lung cancer cell lines exposed to carbon ions. Materials and methods The dose-dependent survival rates of seven cell lines exposed to carbon ions, fast neutrons, and photons were obtained using colony-forming assays in vitro. The relative biological effectiveness (RBE) of carbon ions and fast neutrons to photons was determined by comparing the doses at the 10% and 1% survival levels. Results The RBEs at 13, 40, 50, and 80 keV/μm were 1.20–1.29, 1.55–1.80, 1.57–2.00, and 1.69–2.58, respectively, at the 10% survival level. The RBE of 290 MeV carbon ions increased with increasing linear energy transfer. The biological dose (relative physical dose × RBE) distributions in the SOBP did not statistically differ at the proximal, mid, or distal points at the 10% (p = 0.945) and 1% (p = 0.211) survival levels, respectively; however, deviation of the biological dose at 10% and 1% survival were 3%–16% and 6%–24%, respectively. Furthermore, 290 MeV carbon ions at 80 keV/μm in the SOBP were nearly equivalent to 30 MeV fast neutrons. Conclusion Our results demonstrate nearly homogeneous effectiveness in the SOBP, although we are aware of the deviation in some cell lines.     

Cell population kinetics in radiation therapy: relationship of cellular surviving fraction to RBE and OER.

A two-component multitarget model of cellular radiation lethality was used to predict the effects of changing LET and oxygenation. It was assumed that with high-LET radiations there is a greater probability of direct and irreparable events and that hypoxia reduces the number of chemically-mediated indirect and reversible events. Cellular surviving fractions, relative biological effectiveness, and oxygen enhancement ratios were computed on this basis and compared with published experimental data. The model and program were then used to generate isoeffect curves for photons and neutrons, oxygenated and anoxic states, and various specific tissues and tumors.     

Survival and initial chromatid breakage in normal and tumour cells exposed in vitro to gamma rays and carbon ions at the HIRFL

Human hepatoma and normal liver cells were irradiated with (12)C(6+) ion beams (linear energy transfer (LET) = 96 keV microm(-1)) and gamma-rays at the Heavy Ion Research Facility in Lanzhou (HIRFL). The numbers and types of chromatid breaks were detected using the premature chromosome condensation technique. Irradiation with (12)C(6+) ions produced a majority of isochromatid break types, while chromatid breaks were dominant for irradiation with gamma-rays. Experimental results showed that the initial level of chromatid breaks is clearly related to the absorbed dose from (12)C(6+) ions and gamma-rays. The (12)C(6+) ions are relatively more effective at inducing initial chromatid breaks when compared with the gamma-rays. A relative biological effectiveness (RBE) of about 2.5 resulted for the induction of initial chromatid breaks by (12)C(6+) ions relative to gamma-rays in both cell lines.     

Microdosimetric calculation of penumbra for biological dose in wobbled carbon-ion beams with Monte Carlo Method

In carbon-ion radiotherapy, it is important to evaluate the biological dose because the relative biological effectiveness values vary greatly in a patient’s body. The microdosimetric kinetic model (MKM) is a method of estimating the biological effect of radiation by use of microdosimetry. The lateral biological dose distributions were estimated with a modified MKM, in which we considered the overkilling effect in the high linear-energy-transfer region. In this study, we used the Monte Carlo calculation of the Geant4 code to simulate a horizontal port at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. The lateral biological dose distributions calculated by Geant4 were almost flat as the lateral absorbed dose in the flattened area. However, in the penumbra region, the lateral biological dose distributions were sharper than the lateral absorbed dose distributions. Furthermore, the differences between the lateral absorbed dose and biological dose distributions were dependent on the depth for each multi-leaf collimator opening size. We expect that the lateral biological dose distribution presented here will enable high-precision calculations for a treatment-planning system.     

Biological characteristics of carbon-ion therapy

Purpose: Radiotherapy using charged and/or high-linear energy transfer (LET) particles has a long history, starting with proton beams up to now carbon-ions. Radiation quality of particle beams is different from conventional photons, and therefore the biological effects of high-LET irradiation have attracted scientific interests of many scientists in basic and clinical fields. A brief history of particle radiotherapy in the past half-century is followed by the reviewed biological effectiveness of high-LET charged particles.

Results: The latter includes 54 papers presenting 506 RBE (relative biological effectiveness) values for carbon ions and a total of 290 RBE values for other ions identified from 48 papers. By setting a selection window of LET up to 100 keV/μm, we fitted a linear regression line to an LET-RBE relation. The resulting slope of the regression line had a dimension of μm/keV, and showed different steepness for different cells/tissues and endpoints as well. The steepest regression was found for chromosome aberration of human malignant melanoma while the shallowest was for apoptosis of rodent cells/tissue. Both tumour and normal tissue showed relatively shallower slopes than colony formation.

Conclusions: In general, there is a large variation of slope values, but the majority (25 out of 29 values) of data was smaller than 0.05 μm/keV.     

Neutrons applications in cancer treatment and in specific diagnostics

The major effect of ionizing radiation in cells is to destroy the ability of cells to divide by damaging their DNA strands. Extensive researches are leading to an understanding that the characteristics of high LET radiations such as fast neutrons and low LET radiations like protons, photons and electrons are different; because of different types of their interactions with tissue. Low LET radiations mostly damage tissue by producing free radicals. Oxygen has an effect of enhancing free radical formation in cells. Indeed hypoxic cells, which exist in malignant tumors, are radio resistant under irradiation with low LET radiations. In contrast, neutron interacts with tissue primarily via nuclear interactions, so its biological effectiveness is not affected on the presence of oxygen. The required dose to kill the same number of cancerous cells by neutrons is about one third in comparison with photons. Clinical reports show that a full course of treatment with neutrons consists of 12 treatment sessions, compared to 30-40 treatments with photons or electrons. In conclusion, in this review we describe which cancers or tumors could be better treated with neutrons. We also refer to whether neutrons could be used for diagnosis.     

Impact of carbon ion irradiation on epidermal growth factor receptor signaling and glioma cell migration in comparison to conventional photon irradiation

Abstract

Purpose: Radiotherapy of malignant gliomas may be limited by an interference of radiation with the migratory potential of tumor cells. Therefore, the influence of conventional photon and modern carbon ion (¹²C) irradiation on glioblastoma cell migration and on epidermal growth factor receptor-related (EGFR) signaling was investigated in vitro.

Materials and methods: EGFR overexpressing glioblastoma cell lines U87 EGFR++ and LN229 EGFR++ were irradiated with 0, 2 or 6 Gy photons or ¹²C heavy ions. Migration was analyzed 24 h after treatment in a standardized Boyden Chamber assay. At different time points EGFR, protein kinase B (PKB/AKT) and extracellular signal-related kinases (ERK1/2) were analyzed by Western blotting.

Results: 2 Gy photon irradiation increased U87 EGFR++ migration and decreased motility of LN229 EGFR++ cells. Heavy ions decreased migration of both cell lines as a function of dose. There was a time-dependent increase of phosphorylation of EGFR, AKT and ERK1/2 in U87 EGFR++ after 2 Gy photon irradiation. After heavy ion irradiation EGFR, AKT or ERK1/2 remained unchanged.

Conclusions: Results suggest that the impact of irradiation on tumor cell migration depends on radiation type and cell line. Photons, but not heavy ions, potentially contribute to treatment failure by increasing EGFR-related tumor cell migration.     

Radiobiologic basis of the quality factor of protons and helium ions

Reported data and experimental results of measuring the relative biological effectiveness of protons of different energies and helium ions of 4 GeV/nuclon were analyzed to determine quality factors of the major components of cosmic radiations. It is recommended to use quality factors equal to 1.30-1.45 for 100-730 MeV protons and equal to 1.75 for 9 GeV protons and 4 GeV/nuclon helium ions. It is also suggested to employ them as standards for solving practical problems of radiation safety in space flights.