238Puα粒子辐射体体外诱发大鼠肺成纤维细胞恶性转化

本文报告了²³⁸Puα粒子辐射体体外诱发成年Wistar大鼠肺成纤维细胞(WAL-F₁)转化的特征.初步结果表明,在0.01～1.0Gy剂量范围内,细胞的剂量-存活曲线符合单次击中单靶模型:S=e^-D/Do,Do=0.172Gy,没有肩峰剂量(D_q).高LETa粒子(5.25MeV)辐射后早期(第2代)细胞增殖能力明显受抑制,传至第11代后,增殖能力增强,并观察到细胞形态学和生物学的某些转化特征.转化后的细胞经免疫抑制的同种动物体内接种可形成肿瘤.²³⁸Puα粒子与X射线比较,以Do值为生物学终点,α粒子的相对生物效应(RBE)约1l～13.     

γ射线和甲基胆蒽对诱发人胚肺细胞转化的合并作用

本文报告了⁶⁰Coγ射线与3-甲基胆蒽体外联合处理诱发二倍体人胚肺细胞系(HEL-8315)转化的某些生物学和形态学特征。结果表明, 当γ射线(1.0Gy)与3-McA(1.0μgg/m1)二者联仑处理时, 细胞转化率明显增加.细胞形态及生物学特性不同于对照组、溶剂(二甲Ⅱ砜)组、McA组及辐射组：(1)染色体畸交率明显增高, 亦见有单体断裂；(2)在半同体琼脂培养基中形成集落能力增强, 集落形成率高于其他组, (3)形成环状转化灶。结果提示二者鞋合处理时有某种程度的协同效应。     

137Csγ射线诱发BALB/3T3细胞转化及CA和UDS分析

用剂量分别为1、3和5Gy¹³⁷Csγ射线照射培养的BALB/3T3细胞。结果表明，γ射线可单独诱发BALB/3T3细胞转化，其转化率分别为14.56、25.08和24.81 × 10^-3(活细胞);照后第一分裂周期的染色体畸变(CA)率分别为13.5,22.5和41.5%,³H-TdR掺入S期外DNA合成(程序外DNA合成，UDS)的百分数分别为15.2, 32.6和87.3.姐妹染色单体互换(SCE)变化不明显.     

用染色体畸变研究AT细胞系辐射敏感性和适应性反应

目的探讨毛细血管扩张运动共济失调症(ataxiatelangiectasia,AT)细胞系的辐射敏感性和对低剂量辐射能否诱导细胞遗传学适应性反应。方法用2cGy60Coγ射线预先照射进入G1期的AT5B1VA(AT)细胞和GM0639(GM)细胞,培养6h后再照射1.0Gy或3.0Gy60Coγ射线,分析染色体畸变。结果G1期的GM细胞在预照射2cGy60Coγ射线的诱导剂量后能非常显著地降低随后照射1.0Gy或3.0Gy60Coγ射线诱发的染色体畸变率,染色体畸变的观察值非常显著地低于预期值(P<0.001),而对AT细胞则没有观察到这种现象,染色体畸变的观察值与预期值差异无统计学意义(P>0.05);另外,1.0Gy或3.0Gy60Coγ射线诱发AT细胞的各种畸变率(包括着丝粒畸变、无着丝粒畸变和染色单体型畸变)均显著地高于GM细胞(P<0.001)。结论低剂量电离辐射不能诱导AT细胞产生细胞遗传学适应性反应;AT细胞对电离辐射诱发染色体畸变高度敏感,可能是由于不能正确修复DNA双链断裂的结果。     

全身伽玛刀适形放疗非小细胞肺癌169例临床分析

目的 分析非小细胞肺癌(NSCLC)全身伽玛刀适形放疗的疗效及并发症.方法 采用全身伽玛刀治疗的NSCLC 169例,根据病程、肿瘤部位、性质、体积确定放射总剂量、分割次数、时间.小靶区(肿瘤＜3cm),5～10Gy/次,40～50Gy/4～10次;中靶区(肿瘤3～5cm),4～8Gy/次,48～56Gy/4～16次;大靶区(肿瘤≥5cm),3～4Gy/次, 40Gy/10～14次后缩野,追加剂量10～30Gy.结果 完全缓解率(CR)41.6%,部分缓解率(PR)42.8%,无变化率(NC)13.8%,总有效率(CR PR)84.4%.1年局部控制率92.3%,1、2年生存率75.1%、46.2%,放射性肺炎发生率Ⅰ～Ⅱ级为15.4%,Ⅲ级为3.1%.结论 全身伽玛刀治疗NSCLC近期疗效好,副作用轻微,能显著提高肿瘤的局部控制率.     

碳离子放射治疗肌层浸润性膀胱癌Ⅰ/Ⅱ期临床研究的初步疗效观察

目的 评估Ⅰ/Ⅱ期临床研究中碳离子放疗(CIRT)治疗肌层浸润性膀胱癌的可行性和安全性。方法 研究对象为2020年3月至2022年1月就诊甘肃省武威肿瘤医院的9例肌层浸润性膀胱癌患者(不伴远处转移),临床分期为T_2~3。治疗包括3分次,由12 Gy增加到24 Gy的局部照射和11分次44 Gy的全膀胱照射。碳离子照射剂量均为相对生物学有效性(RBE)为3.0时的剂量。膀胱肿瘤总剂量为56~68 Gy,分14次。主要观察终点包括肿瘤的治疗相关不良反应和剂量限制毒性(DLT)、局部控制率(LC)。次要终点为无进展生存期(PFS)。结果 9例患者完成了试验研究中各剂量段CIRT,剂量递增至68 Gy。未发生DLT和≥3级的急性放疗不良反应和生存期内的晚期放疗不良反应。肿瘤剂量达到68 Gy时,出现2例2级急性泌尿生殖道反应,1例急性下消化道症状;62 Gy以上剂量组观察到3例1级晚期放射性膀胱反应,表现为尿频和镜下血尿。所有病例治疗结束时血尿均消失,排尿不畅缓解,尿红细胞值显著下降。治疗后3个月、6个月局部控制率分别为100%和88.9%,客观缓解率均为88.9%。1例患者在治疗后6个月出现局部复发,采用挽救性手术治疗。结论 碳离子放射治疗肌层浸润性膀胱癌初步疗效观察,未见剂量限制性毒性,安全可行,近期疗效显著,症状缓解明显,患者耐受性好。     

137Cs γ射线诱发CHL细胞遗传不稳定性

目的 研究辐射诱发的CHL细胞遗传不稳定性在基因、染色体及细胞水平上的传递及表达情况。方法 不同剂量一次照射CHL细胞,于不同时间点分析受照存活细胞的HGPRT位点突变、微核及细胞凋亡。结果 CHL细胞照射3Gy后53天,其后代仍表达出显着升高的HG PRT位点突变率。细胞照射3Gy后6小时的双核细胞微核率达(41.51±3.61)%,3天后下降为(14.47±2.39)%,56天后为(10.51±0.87)%,显着高于对照组(P<0.01);而受照细胞子代双核率无显着变化,接种效率明显降低(3Gy剂量以上P<0.01).细胞受照射3、4、6、9、10Gy后,第2天细胞凋亡率达最大值,10Gy剂量组为(24.90±6.72)%,之后各剂量组细胞凋亡率迅速下降,但直到照射后12天细胞凋亡率仍维持在10%左右,显着高于对照组(P<0.01).结论 辐射诱发的细胞基因组不稳定性可以表现在基因、染色体及细胞等不同水平上,推测在其产生和传递过程中可能伴随着某些基因的改变。     

低剂量X射线诱导离体人淋巴细胞染色体损伤的适应性反应

适应性反应的存在已被广泛证实,但主要是通过染色单体型畸变或SCE(姐妹染色单体互换)指标证实的.本文试图对低剂量(简称D_1)辐射如何影响DNA复制前大剂量(D_2)辐射诱发体型染色体畸变进行观察.实验用健康成年人静脉血淋巴细胞,分成三组.(1)G_0期(加PHA前)照射D_1后间隔0、3、5、7和9h再照射D_2;(2)G_1期照射D_1后间隔0,3,5,7和9h再照射D_2.(1)、(2)组用的D_1和D_2分别为0.02Gy和3.0Gy X射线;(3)用标记BrdU(5-溴脱氧尿嘧啶核苷)法分析G_0和G_1期受0.01～0.10Gy X射线照射后细胞动力学变化.结果:1.染色单体型畸变率在G_0和G_1期受D_1     

MRS在星形细胞肿瘤术后放疗中的价值:Cho/Cr的变化及意义

目的:研究星形细胞肿瘤术后、分次放疗后急性期及早期迟发反应期MRS上Cho/Cr随剂量、时间的变化趋势。方法:共18例,年龄9~67岁(平均46±14岁),采用GE signa VH/i 3.0T成像系统进行检查,MRS采用多体素PRESS序列。均为术后患者(全切或部分切除),其中胶质母细胞瘤(WHO 4级)7例,间变性星形细胞瘤(WHO 3级)4例,弥漫性星形细胞瘤(WHO 2级)6例,毛细胞型星形细胞瘤(WHO 1级)1例。测量两个体素:≥60Gy区(肿瘤床区)和<40Gy区(对侧正常区)。一般先行常规分割放射治疗,然后进行调强适形放射治疗,靶区总处方剂量为60~68Gy。结果:≥60Gy区的Cho/Cr在放疗至60%总剂量时已经开始降低,并且呈进行性降低(从治疗前的2.521降到治疗后1个月的1.810)。而<40Gy区则先轻度升高,随后降至原来的水平。结论:MRS的Cho/Cr可以对星形细胞肿瘤术后、放疗后急性期和早期迟发反应期的代谢物改变进行检测,有利于对肿瘤治疗后的早期反应进行有效评估。     

~(238)Puα粒子诱发C3H10T1/2转化细胞的成瘤性能力弱于X射线

C3H10T1/2细胞转化后失去接触抑制,并形成多层生长,易与接触抑制的单层细胞相互区别。用C3H10T1/2小鼠细胞经238　Puα粒子或X射线照射后的转化试验比较二者诱发C3H10T1/2细胞转化的成瘤性。方法:α粒子的照射能量为3.26±0.22MeV,在水中的LET值为121keV/μm。X射线照射条件为420kVp,电压250kV,电流15mA。5GyX射线照后C3H10T1/2细胞的存活率为0.2±0.02,转化率为(8.3±1.4)×10-4/存活细胞,1Gyα粒子照后细胞存活率为0.25±0.03,转化率为(11.1±1.6)×10-4/存活细胞。照射后挑取复层生长的细胞集落(α粒子诱导的集落58个,X射线…     

高 LET 和低 LET 辐射体外诱发细胞恶性转化的比较

目的本研究采用体外细胞转化系统，比较观察了高ＬＥＴ（２３８Ｐｕα粒子，５．２５ＭｅＶ）和低ＬＥＴ（Ｘ射线，１８０ｋＶ）辐射体外诱发成年大鼠肺成纤维细胞系（ＷＡＬ－Ｆ１）恶性转化的特点。方法①应用体外细胞转化模型；②观察指标包括转化细胞形态学和生物学特性的改变；③转化细胞在体内的致瘤作用等。结果α粒子和Ｘ射线诱发同一细胞系转化的形态学与生物学特性基本相似，但在生物学效应上二者存在以下的差异：①细胞存活曲线模型，α粒子为单击单靶模型，Ｄ０值为０．１７２Ｇｙ；Ｘ射线为单击多靶模型，Ｄ０值为１．６６Ｇｙ；②对细胞增殖能力、染色体畸变及集落形成率的影响，产生相近的生物效应所需的剂量，α粒子比Ｘ射线约低１０倍；③以在动物体内致瘤性为终点，引发肿瘤的剂量，α粒子对Ｘ射线的ＲＢＥ值为６（３．０／０．５）。结论实验表明，高ＬＥＴ对体外细胞亦具有较高的致瘤效应。     

Study on cell survival, induction of apoptosis and micronucleus formation in SCL-II cells after exposure to the auger electron emitter (99m)Tc

OBJECTIVE: To study the biological effectiveness of Auger electrons emitted by (99m)Tc on cell survival, induction of apoptosis and micronucleus (MN) formation in the human squamous cell carcinoma cell line SCL-II and compare the effects observed to those observed after exposure to external 60Co gamma radiation. MATERIAL AND METHODS: Cells were either gamma(60Co)-irradiated (0.67 Gy/min) or exposed to (99m)Tc-pertechnetate (0.95-14.3 MBq/ml) for 24 h under cell culture conditions and assayed for cell survival (colony-forming assay), micronucleus formation (cytochalasin B assay) and the frequency of apoptotic cells (fluorescence microscopy). Monte Carlo based dosimetry has been applied to derive the absorbed dose corresponding to the accumulated decays of (99m)Tc under the given geometry. RESULTS: Absorbed doses up to 0.5 Gy could be achieved after 99mTc-exposure leading to no substantial cell killing in this dose range except at one dose point (0.1 Gy) resulting in an relative biological effectiveness (RBE)SF 0.9 of 0.64 when compared to the 60Co reference radiation. MN formation was described best by a linear dose response and was consistently lower after 99mTc exposure when compared to 60Co irradiated cells resulting in an RBE of 0.37. Apoptosis induction was significantly increased after 99mTc exposure at much lower doses (0.1 Gy) when compared to the reference radiation. The (99m)Tc uptake experiments revealed an activity concentration ratio cells vs. medium of 0.07 after 24 h of exposure. CONCLUSION: No overall increased biological effectiveness due to the emitted Auger electrons of (99m)Tc, applied as sodium-pertechnetate, could be observed in the investigated cell line when compared to acute external gamma radiation. The RBEs in the range of 0.37-0.64 might be well explained by dose rate effects. The significantly increased apoptotic response after (99m)Tc-exposure at very low doses has to be further investigated.     

Effekte von Fraktionierung und Dosisleistung bei der PDR-Brachytherapie von B14-Zellen

Purpose

Present radiobiological studies for different cell lines in vitro demonstrate the equivalence and efficacy of continuous low-dose-rate brachytherapy (LDR-BT) and pulsed dose rate brachytherapy (PDR-BT) when using small and frequent dose pulses. The aim of this study was to examine monolayer fibroblast cultures in vitro to examine the biological effects of different pulse doses and dose rates under clinically conditiones.

Material and Methods

B14 cells, Hy B14 FAF 28, peritoneal fibroblasts, were cultured in multi-well plates and exposed to a PDR radiation source at a distance of 9 mm. The following PDR-schemes were compared: dose per pulse: 1 Gy, 2.5 Gy and 5 Gy to a total dose of 5 Gy/5 h (overall time). 10 Gy/10 h, 20 Gy/20 h and 30 Gy/30 h. The pulse duration for the examination of dose rate effects was 20 min, 30 min or 52 min corresponding to a pulse dose rate of 300 cGy/h, 200 cGy/h or 115 cGy/h. Treatment endpoints were cell survival measured by dye exclusion test and clonogenic cell survival.

Results

Cell survival decreased for pulse doses of 5 Gy compared to 2.5 Gy or 1 Gy per pulse (mean dose rate 200 to 300 cGy/h). No differences were observed with dose rates during irradiation of 300 cGy/h, 200 cGy/h or 115 cGy/h (20 Gy/l Gy).

Conclusion

Radiobiological effects of PDR-BT are dependent on the dose per pulse, with differences in biological effects only with a dose per pulse of more than 2.5 Gy, considering the described in-vitro conditiones. More examinations with a more pronounced difference in dose rate will be continued for evaluation of dose rate effects.     

Induction of cytogenetic adaptive response of somatic and germ cells in vivo and in vitro by low-dose X-irradiation

The cytogenetic adaptive response induced by low-level radiation was studied using human and rabbit lymphocytes in vitro and bone marrow cells and germ cells in vivo. The inductive dose of X-rays was 10 mGy for the in vitro studies at a dose rate of 10 mGy/min, and 2, 10, 50, 75 and 100 mGy for the in vivo studies at a dose rate of 50 mGy/min. The challenging dose was 1.5 Gy X-rays for the in vitro experiments and 0.65 or 0.75 Gy for the in vivo experiments at a dose rate of 0.44 Gy/min. The results reported here, in addition to those that have appeared in the literature, show the following characteristics documented for the first time: (1) 10 mGy could induce the adaptive response in human as well as rabbit lymphocytes irradiated not only in G1, S and G2 phases, but also in the Go state; (2) although the induced adaptive response could only last three cell cycles, it could be revived when the inductive dose was repeated after the third cell cycle; (3) the adaptive response could be induced by low-dose X-rays in somatic cells, both in vitro (lymphocytes) and in vivo (bone marrow cells), and also in germ cells (spermatocytes); (4) the magnitude of the adaptive response induced by whole-body irradiation was found to be dose-dependent--the lower the inductive dose the more the reduction of the frequency of chromatid aberrations following the challenging dose.     

Lack of inverse dose-rate effect on fission neutron induced transformation of C3H/10T1/2 cells

Exponential and density-inhibited cultures of C3H/10T1/2 cells were exposed to a single dose of 0.3 Gy of fission neutrons delivered at rates ranging from 0.005 to 0.1 Gy/min. No discernible effect upon cell survival or transformation was observed by a lowering of the fission neutron dose rate in either exponential or plateau cultures. At the level of 2.3 x 10(-4) transformants per surviving cell, the RBE for neoplastic transformation was three at acute dose rates and ten at the lowest dose rate studied (0.005 Gy/min for neutrons and 0.01 Gy/min for X-rays).     

High dose rate and flattening filter free irradiation can be safely implemented in clinical practice

Purpose: We hypothesize that flattening filter free (FFF) high dose rate irradiation will decrease cell survival in normal and cancer cells with more pronounced effects in DNA repair deficient cells. Additionally, we hypothesize that removal of the flattening filter will result in an enhanced relative biological effectiveness independent of the dose rate.

Materials and methods: Clonogenic survival was assessed after exposure to dose rates of 4 or 24 Gy/min (FFF 10 megavolt [MV] photon beam) using a Varian TrueBeam accelerator. Additionally, cells were exposed to 4 Gy/min with or without flattening filter. Relative biological effectiveness estimations were performed comparing the different beam photon spectra.

Results: Cell survival in tumor and normal cell lines was not influenced by high dose rate irradiation. The intrinsic radiation sensitivity of DNA repair deficient cells was not affected by high dose rate compared to normal dose rate. Furthermore, the relative biological effectiveness was not significantly different from unity in any of the cell lines for both FFF and conventional flattened beam exposures.

Conclusions: High dose rate irradiation did not affect long-term survival and DNA repair for cell lines of different tissues. This suggests that high dose rate does not influence treatment outcome or treatment toxicity and could be safely implemented in clinical routine.     

Der Einfluss ionisierender Strahlen auf die Entwicklung der Sekundärkatarakt in vitro

BACKGROUND AND PURPOSE: Histologically, the posterior capsule opacification (PCO) corresponds to regenerative tissue of transformed lens epithelial cells (LECs) with extracellular matrix production. In this study, the influence of ionizing radiation on proliferating LECs and the development of PCO was investigated in vitro. MATERIAL AND METHODS: Each four and 14 pork lenses, respectively, were irradiated with 6 MeV electrons with single doses of 8, 10, 12, and 20 Gy. 1-2 h after irradiation the lens was removed by capsulorrhexis and hydrodissection. After fixation of the capsular bag in a special device the proliferation of residual LECs was examined daily. The experiment was considered to be finished when the capsular bag was completely opacified by confluent cell proliferates. RESULTS: Single dose irradiation with electrons in a dose range from 8 to 12 Gy significantly protracted the development of PCO with complete inhibition of PCO after application of 20 Gy. CONCLUSION: To inhibit PCO in vitro, a single dose of 20 Gy is necessary. The actual in vitro model allows an optimal investigation of PCO formation under different external influences and is therefore very suitable for radiobiological questions.     

211At-αDose Dependence of Poly-ADP-Ribosylation of Human Glioblastoma Cells in Vitro Suitability in Cancer Therapy?

AIM: It was intended to test the biological response (poly-ADP-ribosylation of cellular proteins) of alpha-particles from extracellular 211At for enhanced damage to human glioblastoma cells in vitro and to discuss its suitability for potential application in therapy of high-grade gliomas. MATERIALS AND METHODS: Confluent cultures of human glioblastoma cells were exposed to different doses of alpha-radiations from homogeneously distributed extracellular 211At. Cellular poly-ADP-ribosylation of all proteins including histones was monitored since it is an indirect but sensitive indicator of chromatin damage and putative repair in both normal and malignant mammalian cells. RESULTS: A significant diminution (average 85.6%) in poly-ADP-ribosylation of total cellular proteins relative to that for non-irradiated glioblastoma cells was observed following 0.025 to 1.0 Gy alpha-radiations. In the dose range of 0.0025 to 0.01 Gy there was an increase with a maximum value of approximately 119.0% at 0.0025 Gy. Below 0.0025 Gy no change in poly-ADP-ribosylation was observed. CONCLUSIONS: Level of cellular poly-ADP-ribosylation of proteins at 0.025 to 1.0 Gy of alpha-radiation dose from 211At appears to cause enhanced damage by creating molecular conditions which are not conducive to repair of DNA damages in human glioblastoma cells in vitro. Therefore, it is assumed that clinical application of 211At at least in this dose range might enhance clinical efficacy in radiotherapy of cancer.     

电离辐射体外诱发细胞转化的形态计量学研究

本研究采用图像分析技术，分别观察＾６０Ｃｏγ射线和＾２３８Ｐｕα粒子辐射诱发人胚肺和大鼠肺成纤维细胞转化的细胞和细胞核形态计量学参数的变化及其与照射剂量间的定量关系。结果表明，两种类型的电离辐射诱发细胞转化的生物学特性及细胞形态学参数的变化基本相。细胞及细胞核的面积、等儿直径和核浆比等随照射剂量增加而增大，可采用线性平方模型表达：Ｅ＝ａ＋ｂＤ＋ｃＤ＾２。这上些参数值的变化还与转化后细胞代龄有关。     

Absence of A Dose-rate Effect in the Transformation of C3H 10T1/2 Cells by α-particles

Summary

The findings of Hill et al. (1984) on the greatly enhanced transformation frequencies at very low dose rates of fission neutrons induced us to perform an analogous study with α-particles at comparable dose rates. Transformation frequencies were determined with γ-rays at high dose rate (0·5 Gy/min), and with α-particles at high (0·2 Gy/min) and at low dose rates (0·83–2·5 mGy/min) in the C3H 10T1/2 cell system.

α-particles were substantially more effective than γ-rays, both for cell inactivation and for neoplastic transformation at high and low dose rates. The relative biological effectiveness (RBE) for cell inactivation and for neoplastic transformation was of similar magnitude, and ranged from about 3 at an α-particle dose of 2 Gy to values of the order of 10 at 0·25 Gy. In contrast to the experiments of Hill et al. (1984) with fission neutrons, no increased transformation frequencies were observed when the α-particle dose was protracted over several hours.