Cell Kinetics and Radiation Biology

Summary

The cell cycle, the growth fraction and cell loss influence the response of cells to radiation in many ways. The variation in radiosensitivity around the cell cycle, and the extent of radiation-induced delay in cell cycle progression have both been clearly demonstrated in vitro. This translates into a variable time of expression of radiation injury in different normal tissues, ranging from a few days in intestine to weeks, months or even years in slowly proliferating tissues like lung, kidney, bladder and spinal cord. The radiosensitivity of tumours, to single doses, is dominated by hypoxic cells which arise from the imbalance between tumour cell production and the proliferation and branching of the blood vessels needed to bring oxygen and other nutrients to each cell.

The response to fractionated radiation schedules is also influenced by the cell kinetic parameters of the cells comprising each tissue or tumour. This is described in terms of repair, redistribution, reoxygenation and repopulation. Slowly cycling cells show much more curved underlying cell survival curves, leading to more dramatic changes with fractionation, dose rate or l.e.t. Rapidly cycling cells redistribute around the cell cycle when the cells in sensitive phases have been killed, and experience less mitotic delay than slowly proliferating cells. Reoxygenation seems more effective in tumours with rapidly cycling cells and high natural cell loss rates. Compensatory repopulation within a treatment schedule may spare skin and mucosa but does not spare slowly proliferating tissues. Furthermore, tumour cell proliferation during fractionated radiotherapy may be an important factor limiting the overall success of treatment.     

Induction of apoptosis in human tumor cells after exposure to Auger electrons: comparison with gamma-ray exposure

To clarify the contribution of apoptosis to cell death in four human solid tumor cell lines, clonogenic cell survival (indicator of radiosensitivity) and induction of caspase-3 (CASP-3)/caspase-3-like proteases (CASP-3LP) and the production of DNA fragmentation (markers for apoptosis) were studied in RKO, LS174T, MCF7 and TE671 cells exposed to DNA-incorporated Auger-electron-emitting ¹²⁵I (5-[¹²⁵I]iodo-2′-deoxyuridine) or γ-radiation. Clonogenic survival was assessed by colony-forming assay, CASP-3/CASP-3LP induction with a fluorogenic substrate and DNA fragmentation by ligation-mediated polymerase chain reaction. For ¹²⁵I, log dose–survival curves had no shoulder [high-linear-energy-transfer (LET)-like] and decreased exponentially at different rates in various cell lines. Induction of CASP-3/CASP-3LP in radiosensitive RKO and LS174T cells was threefold greater than that in radioresistant TE671 and MCF7 cells. Nucleosomal laddering in ¹²⁵I-radiosensitive cell lines was dose-dependent, and no laddering was detected in radioresistant lines. For γ-radiation, the survival curve for LS174T cells was monoexponential and that for the other lines exhibited a distinct shoulder (low-LET-like). The most radiosensitive cell line, LS174T, showed the highest induction of CASP-3/CASP-3LP, and the most radioresistant line, TE671, showed the lowest induction. Although DNA laddering was not detectable in TE671 cells, it was observed in other lines, being most prominent in LS174T cells. We conclude that apoptosis initiated by DNA-incorporated ¹²⁵I is dose-dependent, correlates with cell radiosensitivity and takes place through a CASP-3-mediated pathway, whereas that after γ-irradiation probably occurs via a CASP-3-independent pathway and/or a CASP-3-mediated pathway and does not correlate with cell radiosensitivity.     

清华大学反应堆大动物照射的剂量测定

清华大学游泳池式轻水反应堆1号孔道是国内目前唯一的裂变中子生物辐照场所,通过把不同厚度的铅过滤板横插于入射辐射束中,获得了四种不同中子-γ比释动能比率的混合中子-γ辐射条件,对狗进厅单侧照射。狗体模由TE液体组成,用双电离室方法测量吸收剂量.上述四种混合辐射场的中子-γ比值分别为l 0.6,2.06、1.12和0.16。确定了不同中子-γ比条件下沿水平中心线的深度剂量分布.给出了中心剂量、入射剂量和出射剂量值。按照lCRU10_e报告建议的划分照射均匀程度的指标,四种条件下的大动物(狗)照射都属于非均匀照射.     

Molecular and cellular radiobiology of heavy ions

Quantitative studies at the BEVALAC have demonstrated some of the physical and radiobiological factors that promise to make accelerated heavy ions important for the therapy of cancer. The measured physical dose-biological effect relationships allow the safe and effective delivery of therapeutic schedules of heavy ions. Among the charged particle beams available, carbon, neon and helium ions in the "extended Bragg peak mode" have optimal physical and biological effectiveness for delivery of therapy to deep seated tumors. The depth-dose profiles of these beams protect intervening and adjacent tissues as well as tissues beyond the range of the particles. For the treatment of hypoxic tumors, silicon and argon beams are being considered because they significantly depress the radiobiological oxygen effect in the region of the extended Bragg ionization peak. The depth-effectiveness of the argon beam is somewhat limited, however, because of primary particle fragmentation. Silicon beams have a depth-dose profile which is intermediate between that of neon and argon, and are candidates to become the particle of choice for maximizing high LET particle effects. Heavy accelerated ions depress enzymatic repair mechanisms, decrease variations of radiosensitivity during the cell division cycle, cause greater than expected delays in cell division, and decrease the protective effects of neighboring cells in organized systems. Near the Bragg peak, enhancement of heavy particle effects are observed in split dose schedules. Late and carcinogenic effects are being studied. With the newly developed Repair-Misrepair theory we can quantitatively model most observations.     

Stereotactic Radiosurgery for Benign Brain Tumors: Treatment Rationale and Outcomes

Stereotactic radiosurgery has become a well established territory in the neurosurgical treatment armamentarium. The spectrum of clinical applications of stereotactic radiosurgery has greatly expanded to include a wide variety of benign brain tumors. The radiobiological basis and possible mechanisms for tumor responses following stereotactic radiosurgery treatment have been elucidated. The following sections in this review summarize the reported results of the radiosurgery treatment for the different categories of benign brain tumors. The author concluded the analytical review by proposing a treatment rationale for benign brain tumors in light of the risk-benefit ratios of other available treatment options.     

三种方法检测鼻咽癌细胞株SF2的结果分析

目的：比较三种不同方法检测鼻咽癌细胞株2Gy照射后细胞的存活分数(survival fraction at two grey,SF2)的优劣和结果的相关性。方法：选用4种鼻咽癌细胞株CNE1、CNE2、SUNE、SUNE1,分别用平板克隆形成试验、MTT比色法和微量细胞克隆形成法测定其SF2的值。结果：三种方法测得的SF2值之间有明显的相关性,相关系数分别为0．993、0．994和0．973(P＜0．01)。结论：MTT比色法和微量细胞克隆形成法可以代替传统的克隆形成试验来测定细胞株的SF2,且具有微量、快速、简便、经济等优点。     

Hyperbaric oxygen As a radiation sensitizer in the treatment of brain tumors

Rat brain tumor cells grown in a monolayer culture were irradiated in 1.0, 1.5, and 2.0 atmospheres absolute oxygen pressure. Sensitivity of the cells to radiation was not increased by raising oxygen pressure above 1.0 atmosphere absolute during exposure to radiation.     

Invalidity of,and alternative to,the linear quadratic model as a predictive model for postirradiation cell survival

The linear quadratic (LQ) model has been the dominant tool in preclinical radiobiological modeling of cell survival as a function of dose. However, as a second-order polynomial approximation, it suffers from two well-known pitfalls: nonmonotonic behavior and poor extrapolation. This study examined the raw data of 253 sets of photons and 943 sets of the ion beam from the Particle Irradiation Data Ensemble (PIDE) project to understand how often the LQ model could result in a negative β, which would give unrealistic predictions. Additionally, the predictive performance of the LQ model, the power model, and the linear model's predictive performance was studied using leave-one-out cross-validation (LOOCV) and twofold cross-validation. It was found that, when fitted to the LQ model, 7.5% of the photon and 29.8% of the ion beam dose–response data would result in negative β, compared to 0.77% and 2.0%, respectively, reported in published works. The LQ model performed poorly in LOOCV compared to the alternative power model, and performed the worst among the three models in twofold cross-validation. The LQ model leads to unrealistic parameters, which are vastly under-reported in published studies, and performs poorly in standard cross-validation tests. Therefore, the LQ model is not a valid predictive dose–response model for cell survival. Alternative models need to be investigated.     

原发性肝细胞癌体部立体定向放疗的疗效及安全性

近年来,随着肿瘤放疗技术进展,原发性肝细胞癌(hepatocellular carcinoma,HCC)的放疗引起越来越多的关注,越来越多的证据也表明其较好的疗效。其中,体部立体定向放疗(stereotactic body radiation therapy,SBRT)对于不适合一线手术或经皮射频消融技术的HCC患者,在提高局部控制率方面发挥了重要作用。SBRT的研究已经开展了很多,也获得了明确的疗效。但关于恰当治疗适应证,合理剂量分割等方面的研究仍有限。本文综述SBRT对于不可手术的HCC患者的有效性、安全性、适应证和剂量分割模式。