Huge differences in cellular radiosensitivity due to only very small variations in double-strand break repair capacity

The DNA double-strand break (DSB) repair capacity of normal human fibroblasts was compared with that of cell lines with different genetic alterations. These cell lines are affected either in non-homologous end-joining (180BR), homology directed repair (C2352, C2395), base excision repair (CS1TAN, 46BR) or signalling (AT3, AT2BE, LFS2675, LFS2800, 95P558). Cellular radiosensitivity was determined by colony formation assay, DSB by constant-field gel electrophoresis and apoptosis was detected by caspase3 activity. For the mutated cell lines, the survival fraction at 2 Gy (SF2) varied between 0.013 and 0.49 in contrast to a variation of only 0.15?–?0.53 for normal fibroblasts. There was no variation in the number of initial DSB and only a small variation in the number of DSB remaining 24 h after irradiation. At 100 Gy, the latter number varied between 2 and 5 Gy-equivalents for normal fibroblasts and only between 3 and 7 Gy-equivalents for the mutated cell lines, corresponding to repair capacities of 95?–?98 and 93?–?97%, respectively. There were, however, two outliers (LFS2800, 180BR) where the number of remaining DSB was much higher with 22 and 30 Gy-equivalents, respectively. This elevated number resulted from a delayed repair and apoptotic cells. For all but these two cell lines, the relationship between the number of DSB remaining 24 h after irradiation and SF2 could be described by an identical correlation (r²?=?0.86, p?<?0.0001). This result indicates that the relationship between DSB repair capacity and cellular radiosensitivity appears to be the same for normal and mutated cell lines, and that in both cases huge differences in cellular radiosensitivity result from only a very small variation in DSB repair capacity.     

柔性PET衬底上ZnO薄膜的制备、电学性质及激光辐照效应

室温下采用中频反应磁控溅射技术在柔性PET（Polyethylene terephthalate）衬底上沉积了ZnO薄膜。研究了溅射功率和氩氧流量比对薄膜电学性质的影响,获得室温沉积柔性ZnO薄膜的优化工艺条件为溅射功率20 W和氩氧流量比1：1。采用不同能量密度的激光辐照,有效改善了柔性ZnO薄膜的晶体结构和电学性能。原子力显微镜（AFM）和X射线衍射（XRD）测试结果显示,激光辐照可使薄膜表面ZnO颗粒产生团聚融合,并在（100）和（101）晶面上产生明显的取向生长,薄膜由非晶转为多晶结构。Hall性质的研究结果表明,激光辐照可有效提高ZnO薄膜的载流子浓度,降低电阻率,改善室温沉积柔性ZnO薄膜导电性能。     

Effect of mechanical injury to bone marrow in irradiated mice on dispersion of endogenous colony-forming units

The femur was fractured in mice irradiated in a dose of 600 R and the fragments united by a metal pin. Under these conditions, when part of the bone marrow was destroyed, the number of endogenous colonies in the spleen was increased.Department of General Radiology, Institute of Medical Radiology, Academy of Medical Sciences of the USSR, Obninsk. (Presented by Academician of the Academy of Medical Sciences of the USSR G. A. Zedgenidze.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 70–72, January, 1976.     

辐射引起的小鼠外周血淋巴细胞凋亡及其机理

用原位末端标记、ＤＮＡ电泳和免疫组化技术，观察了经２，４，６和８Ｇｙ不同剂量γ－射线照射后，小鼠外周血淋巴细胞的凋亡和与凋亡有关的Ｂａｘ和Ｂｃｌ－２蛋白在其中的作用。结果表明：（１）在照射后早期（４ｈ～７ｄ），淋巴细胞凋亡率迅速增加，如２，４，６和８Ｇｙ照射后４ｈ，凋亡率分别为对照值的２．６，３．８，５．５和１０．４倍，显示出较好的剂量效应关系。（２）随着照射剂量的增加，淋巴细胞绝对数急剧降低，如２，４，６和８Ｇｙ照射后４ｈ，淋巴细胞的绝对数分别为对照值的８２％，６３％，４７％和２２％，与淋巴细胞凋亡呈相反趋势，提示凋亡可能是急性照射后淋巴细胞减少的主要原因之一。（３）ＤＮＡ凝胶电泳显示，６Ｇｙ照射后３ｄ，淋巴细胞出现特征性的梯形谱；末端标记法显示，６Ｇｙ照射后７ｄ，凋亡率达到峰值，为照前值的１６倍，这些结果与Ｍａｙ－Ｇｒｕｎｗａｌｄ－Ｇｉｅｍｓａ染色所得数据基本符合。（４）照射后Ｂａｘ和Ｂｃｌ－２蛋白的异常表达证实，二者在淋巴细胞凋亡的调控中起重要作用。上述结果为阐明淋巴细胞辐射损伤与修复的机制，以及急性放射病的防治提供了重要的依据。     

Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy

Background

Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH.

Procedure

Retrospective cohort study (1980–2010) of 119 survivors treated with rhGH for irradiation‐induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD.

Results

Median survivor follow‐up since rhGH initiation was 4.8 (range 0.2–18.3) years. SCFE was diagnosed in 10 subjects post‐TBI and none after CI (P < 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211‐fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency.

Conclusions

The markedly greater SCFE incidence rate in childhood cancer survivors with TBI‐associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE. Pediatr Blood Cancer 2013;60:1766–1771. © 2013 Wiley Periodicals, Inc.     

The role of supracricoid laryngectomy for glottic carcinoma recurrence after radiotherapy failure: a critical review

Conclusions.In the near future salvage supracricoid laryngectomy (SCL) will be used more extensively for failures of radiotherapy for glottic carcinoma. Objectives. Primary radiotherapy has been used for patients with early glottic carcinomas in northern Europe and North America for more than half a century. Local recurrences after radiotherapy for glottic malignancies occur in 5–25% for T1 carcinomas and in 15–50% for T2 carcinomas. The classic choice as salvage surgery in cases of glottic squamous cell carcinoma recurrence after irradiation failure is total laryngectomy. The development of extended conservation procedures such as SCL has permitted an increasing number of successful partial laryngectomies that save laryngeal functions after radiotherapy failure. SCL allows the creation of a neo-larynx, permitting both swallowing and speech; in most cases the tracheostoma can be closed. Methods. The electronic database Pubmed was searched without publication date limits. Results. Considering available data (103 cases), 84.5% of the cases treated with salvage SCL for irradiation failure did not present a new local recurrence; laryngeal recurrences after salvage SCL (15.5%) were successfully treated with total laryngectomy in 66.7% of the cases. Tracheostoma closure was possible in all except two cases after a mean period ranging between 12 and 28 days. Swallowing results seemed good, with longer recovery time in irradiated than in non-irradiated patients who underwent SCL. Voice quality determined with psychoacoustic methods had acceptable intelligibility.