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 C-12(6+) ion beams (linear energy transfer (LET) = 96 keV mu m(-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 C-12(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 C-12(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 C-12(6+) ions relative to gamma-rays in both cell lines.

A colorimetric assay for screening microcystin class compounds in aquatic systems

Secondary metabolites produced by water-blooming cyanobacteria in eutrophic waters include some potent hepatotoxins, These compounds also have tumour-promoting properties, attributable to their inhibition and activation of protein phosphatases and kinases respectively. The inhibitory effect of these toxins on protein phosphatases have been employed in a commonly used radiometric assay, involving the use of a P-32-labeled substrate, for the detection and quantitation of these compounds. This paper investigates and describes a colorimetric method in which the activity of protein phosphatase 2A is determined by measuring the rate of colour production from the release of yellow p-nitrophenol using p-nitrophenyl phosphate as the substrate. Results of this study suggest that the colorimetric protein phosphatase inhibition assay is a simple, inexpensive tool for screening substances that may have tumour-promoting characteristics in aquatic systems. The detection limit of the colorimetric method is comparable to the radiometric assay. (C) 1998 Elsevier Science Ltd. All rights reserved.

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.

Injection system design for a hadron therapy synchrotron

A synchrotron is designed for tumour therapy with C6+ ions or proton. Its injector is a cyclotron, which delivers C5+ or H-2(+) ions to the synchrotron. After comparing the methods of the single-turn injection, the multi-turn injection and the stripping injection, this paper chooses the stripping injection method. In addition, the concept design of the injection system is presented, in which the synchrotron lattice is optimized.

Design of synchrotron for hadron therapy

According to the operation and development of radiation therapy in the world, in order to further promote the radiation therapy of tumour in China, a design of a special synchrotron with two super-periodicity for hadron therapy is presented, including lattice, injection system, RF acceleration and slow extraction of the third order resonance. The synchrotron accelerates the proton beam to 250MeV and the carbon beam to 4000MeV/u.

Correlation between initial chromatid damage and survival of various cell lines exposed to heavy charged particles

The biophysical characteristics of heavy ions make them a rational source of radiation for use in radiotherapy of malignant tumours. Prior to radiotherapy treatment, a therapeutic regimen must be precisely defined, and during this stage information on individual patient radiosensitivity would be of very great medical value. There are various methods to predict radiosensitivity, but some shortfalls are difficult to avoid. The present study investigated the induction of chromatid breaks in five different cell lines, including one normal liver cell line (L02), exposed to carbon ions accelerated by the heavy ion research facility in Lanzhou (HIRFL), using chemically induced premature chromosome condensation (PCC). Previous studies have reported the number of chromatid breaks to be linearly related to the radiation dose, but the relationship between cell survival and chromatid breaks is not clear. The major result of the present study is that cellular radiosensitivity, as measured by D-0, is linearly correlated with the frequency of chromatid breaks per Gy in these five cell lines. We propose that PCC may be applied to predict radiosensitivity of tumour cells exposed to heavy ions.

深层治癌重离子束的配送

在辐射治疗应用方面，相比传统体外辐射疗法，高能量的重离子束流有着巨大的优势。近年来，世界上多数重离子治疗中心都对重离子的辐射特性已经进行了深入研究，从2006年起中国科学院近代物理所也开始了重离子辐射治疗肿瘤的临床实验。目前绝大多数重离子治癌中心都采用了包括一对独立的二极铁的束流配送系统，将从加速器引出的笔形束流在肿瘤的各层等深横截面上进行均匀照射。本文重点阐述了HIRFL-CSR重离子治癌装置中的束流配送系统的工作原理和分系统结构，包括深层治癌重离子束运线，终端扫描系统和根据治疗计划生成的扫描路径软件系统。第一部分简单介绍了世界上各大重离子医疗辐射工程，总结了医疗重离子加速器的设计经验，尤其对日本的HIMAC和德国GSI重离子治癌装置进行了详细介绍，同时对新型重离子治癌装置的特点和重离子治癌装置的发展方向进行了介绍。侧重分析研究了束流引出系统、控制系统和扫描系统的工作原理和相关在线设备，详细比较了两种扫描方式的优缺点。第二部分重点介绍了HIRFL-CSR加速器及其重离子辐射应用工程。CSR是中国第一台重离子冷却存储环，其主加速器CSRm是在兰州重离子治癌装置的核心，负责提供对应不同穿透深度不同能量的慢引出束流。兰州近代物理所的治癌临床实验分为三个阶段，其中第一阶段利用HIRFL辐照终端引出的重离子束流对浅层肿瘤进行适形照射。第二阶段利用CSRm引出的重离子束流开展对深层肿瘤的辐照实验，包括动物实验和临床实验。第三阶段在技术成熟后将小型医用重离子加速器向社会推广。第三部分中总结回顾了深层治癌重离子束运线的设计原理和和束运线的磁聚焦结构。对扫描系统（栅扫描和点扫描）进行了计算机模拟和束斑尺寸的控制方式进行了讨论。在重离子深层治癌进行第一次动物实验时，利用位于终端的分条电离室测试了治癌重离子束流的基本参量，得到了引出束流在垂直和水平方向以及束流微结构的品质信息，并用梯度法测量了束流的发射度。这些工作对于模拟不同引出束流情况对应的不同扫描方式时束流照射均匀度很有帮助，也给制定肿瘤的治疗计划提供了一些参考。最后论文还简单介绍了束流的共振引出系统，侧重说明引出束流的特性，提及重离子垂直治疗终端桶型旋转机架的设计

Scale-up of fermentation and purification of recombinant allophycocyanin over-expressed in Escherichia coli

Phycobiliprotein is a photosynthetic antenna pigment found in cyanobacteria, rhodophytes, cryptophytes and certain dinoflagellates, which has been found to have anti-oxidative and anti-tumour activities. In this paper, a recombinant allophycocyanin (rAPC) had been expressed in Escherichia coli for anti-tumour effect. E. coli cells were cultured using glucose fed-batch method to achieve high cell densities. The biomass of rAPC was up to 3.52 g/L broth. The rAPC was purified from soluble E. coli cell lysate employing hydrophobic interaction chromatographic (HIC) method developed at the bench scale using 20 mL column. The process was performed at the pilot scale using 500 mL column for evaluation of scale-up. An amylose affinity column was used to improve the purity of final product in pilot scale purification. The purification process resulted in greater than 98% pure product and yielded up to 2.0 g/kg wet cells at the bench scale and 1.2 g/kg wet cells at the pilot scale. Peptide mapping was used to prove the identity of rAPC purified from bench scale and pilot scale process. Purified rAPC at the pilot scale was found to have remarkable inhibition on S-180 carcinoma in mice. (c) 2005 Elsevier Ltd. All rights reserved.