不同p53功能状态鼻咽癌细胞株的放射生物学特性

目的探讨鼻咽癌细胞不同p53功能状态及其放射生物学特性之间的关系。方法采用脂质体介导的转染方法将携带野生型p53基因的真核表达质粒pC53-SN3，空载体质粒pCMV-NeoBarn分别转染到鼻咽癌细胞CNE1、DNE2中。p53功能检测技术明确细胞转染p53基因前后的p53功能状态。成克隆实验测定细胞存活分数。采用单击多靶模型和线性二次函数模型拟合细胞存活曲线，求出放射生物学参数Do、Dq、N和α、β、α/β、SF2值。结果转染野生型p53基因后鼻咽癌细胞获得正常p53功能。CNE1-pNeo和CNE1-wtp53细胞的％值分别为1．17、1．08Gv；Dq值分别为2．25、1．21Gy；Q值分别为0．13、0．29Gy^-1；SF2值分别为0．765、0．326。CNF2-pNeo和CNE2-wtp53细胞的Do值分别为0、92、0．84Gy；Dq值分别为1．45、1．04Gy；α值分别为0、13、0．76Gy^-1；SF2值分别为0．675、0．156。CNE1、CNE2细胞转染野生型p53基因后，Do、Dq、SF2值均减小，α值增大。结论野生型p53基因转染可以提高p53功能缺陷的鼻咽癌细胞的放射敏感性。     

全反式维甲酸通过磷酸化JNK抑制视网膜母细胞瘤细胞生长

目的：探索重组病毒介导的外源性野生型p53cDNA(Ad-wtp53）对内源性p53基因状态不同结直肠癌细胞的抑制作用是否存在差异，研究p53基因抑制肿瘤细胞增殖的机制。方法：采用MTT法选择Ad-wtp53的最佳转染滴度，分别感染内源性p53基因缺失，突变和正常的3种结直肠癌细胞株，观察比较它们的生长抑制作用。结果：Ad-wtp53在1000MOI时表现出最强的细胞抑制作用，p53缺失细胞株（THC－8908）的抑制效应最明显，3种细胞转染后均发生G0／G1期阻滞，并对不同p53状态细胞G2－M期具有不同的调控作用。结论：外源性野生型p53 cDNA导入可显著抑制结直肠癌细胞生长，使细胞周期停滞于G0／G1期；同时对内源性p53状态不同细胞的生长抑制强度和G2－M期调控作用不同。     

外源p53对人肺癌细胞生长的抑制

目的　观察外源性野生型p53对有p53基因突变的人肺癌细胞系生长的影响。方法　用PCR SSCP及DNA测序 ,选择p53突变的人肺巨细胞癌系 80 1 D。构建野生型p53表达质粒PZiP p53。用基因枪介导外源基因。经G41 8筛选得到转染细胞系 80 1 D p53。用PCR检测外源基因 ,观察转染细胞恶性生长的变化。结果　转染细胞系 80 1 D p53体外长期传代有外源性p53基因存在 ,转染细胞生长明显受到抑制 ,集落形成抑制率达 96% ,裸鼠异种移植致瘤性降低 ,肿瘤生长明显缓慢。结论　外源性野生型p53经基因枪导入有p53基因突变的人肺癌细胞后可长期存在于转染细胞中 ,且明显抑制所转染的癌细胞的恶性生长。     

野生型p53基因对肝癌细胞多药耐药的逆转作用及其相关机制

背景与目的：细胞凋亡的发生机制在肿瘤多药耐药中起重要作用,野生型p53基因是细胞凋亡的激活剂,与肿瘤多药耐药密切相关。本研究旨在探讨野生型p53基因能否实现对肝癌细胞多药耐药的逆转以及逆转的相关机制。方法：构建野生型P53蛋白表达序列的真核表达载体pCR3．1-p53,用脂质体转染技术建立人肝癌细胞Bel-7402的p53转染细胞株,对转染细胞株进行MTT实验,观察p53基因对肿瘤细胞生长的抑制作用和对肝癌细胞对长春新碱（vincristine,VCR）药物敏感性的影响,姬姆萨染色法观察细胞形态,免疫组织化学SP法检测细胞P糖蛋白（P—glycoprotein,P—gp）的表达,逆转录PCR法检测细胞内mdr1、MRP、GSTπ、TopoⅡ mRNA的表达。结果：转染p53的Bel—p53细胞生长明显慢于未转染的Bel-7402细胞。转染野生型p53的Bel-p53细胞在VCR浓度为0．01μg／ml,0．1μg／ml,1．0μg／ml,10μg／ml,25μg／ml时,其药物敏感性增加;VCR作用最佳浓度为1．0μg／ml。形态学检查转染细胞,在VCR作用下细胞数明显减少,细胞散在不成片、细胞高度水肿、胞体不规则突起,可见核固缩、核裂解、核溶解。p53基因对Bel-7402细胞的mdr1／P—gP的表达有明显的抑制作用．对TopoⅡα基因的表达有上调作用,对GSTπ、MRP基因表达没有影响。结论：p53基因对肝癌细胞多药耐药有逆转作用．其逆转机制可能与降低mdr1／P—gp的表达、上调TopoⅡα的表达．从而增加细胞内VCR药物浓度和VCR药效有关。     

miR-6732-3p对鼻咽癌放射抗拒细胞株CNE-2R放射敏感性的影响

目的 探讨miR-6732-3p表达对人鼻咽癌CNE-2R细胞放射敏感性的影响。方法 采用RT-qPCR检测miR-6732-3p在CNE-2和CNE-2R细胞株中的表达。用miR-6732-3p慢病毒转染CNE-2R细胞后，将CNE-2R细胞分为三组，分别为CNE-2R组（正常对照组）、miR-6732-3p NC组（转染对照组）、miR-6732-3p inhibition组（转染组）。RT-qPCR检测各组细胞中miR-6732-3p的表达，CCK-8、流式细胞术和克隆形成实验分别检测转染前后的细胞增殖、凋亡能力及放射敏感性。结果 RT-qPCR检测结果显示，miR-6732-3p在CNE-2R细胞中的表达量明显高于CNE-2细胞（P=0.036）。采用慢病毒转染CNE-2R细胞后，转染组细胞miR-6732-3p 的表达量均较转染对照组和正常对照组低（P＜0.05）。CCK-8法检测结果显示，与两个对照组相比，转染组细胞生长受抑制（P＜0.001）；在不同照射剂量下，转染组细胞的存活分数均明显降低（P＜0.001）。流式细胞仪检测结果显示，未经照射（0 Gy）和接受8 Gy照射后转染组细胞凋亡率均较转染对照组及正常对照组明显升高（P＜0.05）。克隆形成实验结果显示，转染组的放射生物学参数D0、Dq、SF2值均低于两个对照组（P＜0.05）；在不同照射剂量下，转染组细胞存活分数亦低于两个对照组（P＜0.001）。结论 沉默miR-6732-3p可提高鼻咽癌CNE-2R细胞的放射敏感性，为鼻咽癌放射抗拒的分子靶向治疗提供新思路。     

苦参碱通过诱导miR-433-3p表达抑制食管鳞癌放射抵抗

 目的 探讨苦参碱在食管鳞癌中对放射抵抗及miR-433-3p表达的影响。方法 构建miR-433-3p及RAD21过表达和敲减放射抵抗Eca-109R细胞,经不同照射剂量（0 Gy、2 Gy、4 Gy、6 Gy及8 Gy）及不同浓度（0.5 mg/mL、1.0 mg/mL、2.0 mg/mL、3.0 mg/mL、4.0 mg/mL和5.0 mg/mL）苦参碱分别处理转染前后的Eca-109和Eca-109R细胞后,采用qRT-PCR及Western blot检测miR-433-3p及RAD21的表达情况,CCK-8实验检测细胞活性;在Eca-109细胞系中,应用双荧光素酶报告基因实验检测miR-433-3p与RAD21的相互作用。结果 不同浓度苦参碱作用可抑制放疗抵抗细胞Eca-109R的细胞活性,重建其对放射的敏感性（P＜0.05）。miR-433-3p在Eca-109R细胞中低表达（P＜0.05）;敲减miR-433-3p可增强Eca-109R细胞活性,而苦参碱能够解除miR-433-3p敲减对Eca-109R细胞活性的促进作用（F=5.213,P＜0.05）。RAD21在Eca-109R细胞中高表达（P＜0.05）;过表达RAD21可增强Eca-109R细胞活性,并逆转miR-433-3p对Eca-109R细胞活性的抑制作用（F=4.554,P＜0.05）。双荧光素酶报告基因提示miR-433-3p可作用于RAD21的3′UTR区域。结论 苦参碱通过诱导miR-433-3p高表达而抑制RAD21表达,重建食管鳞癌的放射敏感性。     

食管鳞状上皮细胞癌中P53基因突变的PCR-SSCP检测

应用PCR－SSCP银染技术检测了40例食管鳞状细胞癌p53基因第5、6、7和第8外显于的突变情况。结果显示：13例（32．5％）有p53基因突变，突变主要发生在第5和第8外显子，与癌分化程度无明显关系，但伴淋巴结癌转移病例中p53基因的突变率明显高于无转移者（P＜0．05）。本研究提示，p53基因突变存在于中、晚期食管癌中，并可能与食管鳞癌的进展与转移有关。     

腺病毒介导HSV—tk自杀基因联合野生型p53基因对直肠癌细胞的杀伤作用

目的 观察重组腺病毒介导单纯疱疹病毒胸苷激酶（HSV－tk)基因联合人野生型p53基因共转染,对直肠癌细胞杀伤作用。方法 构建重组腺病毒质粒pAdCMV-Link1(tk/p53)、pAdCMV-Link(tik),pAdCMV-Link(p53),分别感染p53炎变的人直肠癌细胞SW837。进行细胞集落形成实验、细胞存活率的测定和裸鼠移植瘤治疗实验,观察HSV－tk/GCV系统与野生p53基因联合对肿瘤细胞的杀伤作用。结果 应用pAdCMV-Link1(tk/p53),pAdCMV-Link(-),pAdCMV-Link(tk),pAdCMV-Link(p53)重组腺病毒感染SW837细胞,加入GCV,各组细胞集落数分别为8、95、40、70。pAdCMV-Link(CD/53)组肿瘤细胞集落形成减少、细胞存活率显著下降（P＜0．01）。裸鼠移植肿瘤生长抑制率分别为76．5％、0．8％、55．8％、23．2％,pACMV-Link(tk/p53)重组腺病毒对肿瘤的抑制作用最强。结论 HSV－tk自杀基因与野生型p53基因共转染,对肿瘤细胞有更强的杀伤作用。     

E1B55kDa缺陷型腺病毒对人肝癌细胞的杀伤研究

目的 探讨E1B55kDa缺陷型腺病毒dl1520对肝癌细胞的体内外杀伤作用。方法 用dl1520分别感染p53基因型不同的人肝癌细胞,感染后第4天用染色的方法检测存活细胞。用RT－PCR检测细胞内p53和p21^Waf-1基因表达的改变,通过检测腺病毒衣壳蛋白hexon基因的表达证实腺病毒的感染。在SCID裸鼠瘤体内注射dl1520,观察dl1520对肝癌细胞的体内杀伤作用。结果 p53基因缺失的肝癌细胞Hep3B对dl1520诱导的细胞毒性作用最敏感,超过60％的细菌被杀伤,而不足20％的PLC／PRF／5（p53基因突变型）和HepG2(p53基因野生型）肝癌细胞被杀伤。腺病毒感染后,HepG2细胞内p53和p21^Waf-1基因表达水平均明显升高。瘤体内注射dl1520,可显著抑制Hep3B裸鼠移植瘤的生长,而对PLC／PRF／5和HepG2的裸鼠移植瘤则无明显的生长抑制作用。结论 E1B55kDa缺失的腺病毒可以选择性地杀伤p53基因缺失的肝癌细胞,是一种潜在的肿瘤治疗手段。     

逆转录病毒介导p53基因对食管癌细胞株的生长抑制作用

目的观察人类野生型p53(wt p53)基因对人食管癌细胞系的抑制作用.方法用逆转录病毒为载体将外源性wt p53基因导入人食管癌细胞系ECA109,通过体外及小鼠体内实验研究转入基因的表达及对肿瘤的抑制作用.结果 p53在转染细胞ECA109/p53中表达水平提高.外源性wt p53基因的导入和表达能使ECA109细胞的生长速率减低,软琼脂集落形成能力下降,G0 G1期细胞比例增加、S期细胞比例降低,凋亡指数升高,裸鼠体内成瘤能力明显下降.结论逆转录病毒载体介导的外源性野生型p53能够抑制人食管癌细胞生长.     

p53 mutation decreased radiosensitivity in rat yolk sac tumor cell lines.

PURPOSE: We reported that two established rat yolk sac tumor cell lines differ in their radiosensitivity by 1.7 fold, and the variation is most likely manifested by the differences seen in their apoptotic response. We investigated the relationship between radiosensitivity and p53 in these cell lines. METHODS AND MATERIALS: We assessed the status of p53 in cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequence analysis, and also analyzed protein expression of p53, p21, and bax as a function of time after irradiation to determine the signal transduction for p53 by immunoblotting. RESULTS: A band shift was observed only in exon 7 for the radioresistant NMT-1R cells and no band shift was detected for the radiosensitive NMT-1 cells. A band shift was confirmed also at the mRNA level. Exon 7 of p53 DNA showed a three base substitution of DNA at codon 267 to 268. Expression of p53, p21, and bax proteins in NMT-1R cells did not change after 10 Gy irradiation; however, in NMT-1 cells, the expression of these proteins was increased from 1-12 h after irradiation. CONCLUSION: A loss of p53 function by radiation-induced mutation of p53 decreased the radiosensitivity in these cell lines.     

Radiosensitivity of human biliary tract cancer cell lines in vitro

The prognosis of biliary tract cancer is still poor. Although a number of clinical studies have suggested a role for radiation therapy in advanced biliary tract cancer, its value remains controversial. Moreover, the intrinsic radiosensitivity of bile duct cancer cell lines has not been described, and the molecular basis for the response of these tumors to ionizing radiation is poorly understood. The present study was designed to examine the intrinsic radiation sensitivity of human biliary tract cancer cells and its relationship to p53 status. Radiation response expressed by the parameters n, D-0, D-10, alpha, beta, (D) over bar (mean inactivation dose), and SF, of seven cell lines derived from gallbladder and bile duct cancers was determined. The results suggest that biliary tract cancer cell lines as a group are relatively radioresistant. The mean X-ray survival parameters for these seven cancer cell lines were D-0=2.13+/-0.29 Gy, D-10=5.73+/-0.59 Gy, (D) over bar=2.76+/-0.25 Gy, alpha=0.25+/-0.03, and SF2=0.54+/-0.05. One of the seven lines was more radiosensitive than the others (D-0=0.77+/-0.02 Gy, D-10=2.95+/-0.06 Gy, (D) over bar=1.57 Gy, alpha=0.35, SF2=0.35+/-0.03). Five of six lines examined expressed mutant p53 including the radiosensitive line; one radioresistant line expressed wild-type p53. Thus, although loss of wild-type p53 expression occurred frequently in these biliary cancer cell lines, radiosensitivity did not correlate with p53 status. In view of the intrinsic radioresistance of this type of tumor cell coupled with the poor tolerance of surrounding normal tissues, maximal surgical debulking and intraoperative radiation therapy may contribute to increased local control over resection and/or conventional fractionated radiotherapy.     

放射抗拒食管癌细胞系的建立及抗拒机制研究

[目的]建立食管癌放射抗拒细胞系模型并观察食管癌细胞经射线反复照射后放射敏感性的变化。[方法]60Coγ射线对食管癌EC9706细胞系进行照射,每次2Gy,共照射30次,采用克隆形成实验等测定所得的EC9706R60细胞亚系及其亲代细胞EC9706的放射敏感性,检测细胞周期特征、细胞凋亡率及SP细胞(side population cells)比例。[结果]与亲代EC9706细胞相比,EC9706R60细胞显示出明显放射抗性,其D0、Dq及N值增大,细胞存活曲线肩区增宽,EC9706R60细胞的放射抗性(D0)是EC9706的1.375倍(P<0.05)。EC9706R60细胞S期比例较其EC9706细胞明显增高(32.1%vs.3.8%),G0/G1期比例则明显下降(67.9%vs.96.2%)。食管癌细胞EC9706在经30Gy照射后12h细胞凋亡达到峰值11.17%,经60Gy照射后降低到最低点0.99%。EC9706R60细胞SP细胞的比例较EC9706明显增高。[结论]EC9706R60细胞显示出与亲代细胞不同的细胞周期特征,放射抗拒性与SP细胞的比例存在一定关联。高的放射诱导凋亡率可能意味着放射越...     

Adenoviral-mediated p53 transgene expression sensitizes both wild-type and null p53 prostate cancer cells in vitro to radiation

Purpose/Objective: The effect of adenoviral-mediated p53 transgene expression on the radiation response of two human prostate cancer cell lines, the p53^wild-type LNCaP and p53^null PC3 lines, was examined. The objective was to determine if this vector sensitizes cells to radiation independently of their p53 status.

Methods and Materials: A recombinant adenovirus-5 vector (RPR/INGN 201, Introgen Therapeutics, Houston, TX) containing a CMV promoter and wild-type p53-cDNA (Ad5-p53) was used to facilitate p53 transgene expression. A multiplicity of infection (MOI) of 10–40 viral particles per cell was used, based on Ad5/CMV/lacz infection and staining for the β-galactosidase reporter gene product. Clonogenic assays were performed to evaluate the degree of sensitization to radiation of viral-transduced cells compared with irradiated nontransduced controls. The relative efficacy of these treatments to induce apoptotic cell death was determined using the TUNEL assay.

Results: The delivery of Ad5-p53 (10 MOI) reduced control plating efficiency from 36.5% to 0.86% in the LNCaP cell line and from 75.1% to 4.1% in the PC3 cell line. After correcting for the effect of Ad5-p53 on plating efficiency, the surviving fraction after 2 Gy (SF2) of gamma-irradiation was reduced over 2.5-fold, from 0.187 to 0.072, with transgene p53 expression in the LNCaP cell line. Surviving fraction after 4 Gy (SF4) was reduced over 4.5-fold, from 0.014 to 0.003, after Ad5-p53 treatment. In the PC3 cell line, Ad5-p53 (40 MOI) reduced SF2 over 1.9-fold from 0.708 to 0.367, and SF4 over 6-fold from 0.335 to 0.056. In both the LNCaP and PC3 cell lines, the combination of Ad5-p53 plus radiation (2 Gy) resulted in supra-additive apoptosis (20% for LNCaP and 15% for PC3 at 50 MOI), above that seen from the addition of the controls; control vector Ad5-pA plus RT (0.15% for LNCaP and 1.44% for PC3), Ad5-p53 alone (28.6% for LNCaP and 21.7% for PC3), RT alone (0% for LNCaP and 0.23% for PC3), or Ad5-pA alone (0.1% for LNCaP and 0.29% for PC3).

Conclusion: The clonogenic survival and apoptosis data demonstrate that p53 transgene expression sensitizes human prostate adenocarcinoma cells in vitro to irradiation. As this effect was observed in both the p53^wild-type LNCaP and p53^null PC3 lines, radiosensitization was independent of p53 status.     

化合物UC2288对CNE-2R细胞体外及裸鼠移植瘤放射敏感性影响

目的:探讨化合物UC2288对CNE-2R细胞及裸鼠移植瘤放射敏感性影响。方法:化合物UC2288浓度参照以往实验结果(IC 50＝12.20 μmol/L),克隆形成实验检测UC2288联合2、4、6、8 GyX线照射对CNE-2R细胞放射敏感性影响。CCK8实验检测UC2288联合X线2、4、6、8 G...     

Adenoviral-mediated p53 transgene expression sensitizes both wild-type and null p53 prostate cancer cells in vitro to radiation

Purpose/Objective: The effect of adenoviral-mediated p53 transgene expression on the radiation response of two human prostate cancer cell lines, the p53^wild-type LNCaP and p53^null PC3 lines, was examined. The objective was to determine if this vector sensitizes cells to radiation independently of their p53 status.Methods and Materials: A recombinant adenovirus-5 vector (RPR/INGN 201, Introgen Therapeutics, Houston, TX) containing a CMV promoter and wild-type p53-cDNA (Ad5-p53) was used to facilitate p53 transgene expression. A multiplicity of infection (MOI) of 10–40 viral particles per cell was used, based on Ad5/CMV/lacz infection and staining for the β-galactosidase reporter gene product. Clonogenic assays were performed to evaluate the degree of sensitization to radiation of viral-transduced cells compared with irradiated nontransduced controls. The relative efficacy of these treatments to induce apoptotic cell death was determined using the TUNEL assay.Results: The delivery of Ad5-p53 (10 MOI) reduced control plating efficiency from 36.5% to 0.86% in the LNCaP cell line and from 75.1% to 4.1% in the PC3 cell line. After correcting for the effect of Ad5-p53 on plating efficiency, the surviving fraction after 2 Gy (SF2) of gamma-irradiation was reduced over 2.5-fold, from 0.187 to 0.072, with transgene p53 expression in the LNCaP cell line. Surviving fraction after 4 Gy (SF4) was reduced over 4.5-fold, from 0.014 to 0.003, after Ad5-p53 treatment. In the PC3 cell line, Ad5-p53 (40 MOI) reduced SF2 over 1.9-fold from 0.708 to 0.367, and SF4 over 6-fold from 0.335 to 0.056. In both the LNCaP and PC3 cell lines, the combination of Ad5-p53 plus radiation (2 Gy) resulted in supra-additive apoptosis (20% for LNCaP and 15% for PC3 at 50 MOI), above that seen from the addition of the controls; control vector Ad5-pA plus RT (0.15% for LNCaP and 1.44% for PC3), Ad5-p53 alone (28.6% for LNCaP and 21.7% for PC3), RT alone (0% for LNCaP and 0.23% for PC3), or Ad5-pA alone (0.1% for LNCaP and 0.29% for PC3).Conclusion: The clonogenic survival and apoptosis data demonstrate that p53 transgene expression sensitizes human prostate adenocarcinoma cells in vitro to irradiation. As this effect was observed in both the p53^wild-type LNCaP and p53^null PC3 lines, radiosensitization was independent of p53 status.     

抑癌基因p53对人胃癌细胞系放射敏感性的作用

目的评价野生型抑癌基因（正常）ｐ５３对人胃癌细胞系放射敏感性的控制作用。方法用流式细胞仪分析４Ｇｙ照射后８和２４小时４种不同ｐ５３状态的人胃癌细胞系细胞周期分布和凋亡的反应。以４Ｇｙ细胞存活份数和１０Ｇｙ照射后的肿瘤生长曲线比较４种细胞的放射敏感性。结果照射４Ｇｙ后８小时和２４小时的ｐ５３正常的ＢＧＣ８２３细胞出现强烈的Ｇ１期阻滞（分别占原细胞总数的６７．９％和６１．１％）,比无照射的该细胞Ｇ１期比例有显著的增高（Ｐ＜０．０５）,并出现明显的预示凋亡的亚Ｇ１峰（ＳｕｂＧ１）,凋亡细胞比例分别达１３．０％和１５．３％;同样条件下其他３种ｐ５３异常的细胞Ｇ１期比例没有显著的变化（Ｐ＞０．０５）,都没有出现亚Ｇ１峰,凋亡细胞比例均为０．０％。ｐ５３正常的ＢＧＣ８２３细胞４Ｇｙ的存活份数明显低于其它３种细胞（Ｐ＜０．０５）;且细胞移植肿瘤１０Ｇｙ照射后比其它３种的生长受到更明显抑制（Ｐ＜０．０５）。结论以上的结果证实了野生型ｐ５３基因促进了照射后肿瘤细胞的Ｇ１期阻滞和凋亡,从而明显地提高肿瘤细胞的放射敏感性。     

Response of human tumor cells of varying radiosensitivity and radiocurability to fractionated irradiation.

The cytotoxic effects of radiation delivered in daily fractions of 2.0 Gy were examined in plateau phase cultures of human tumor cells of varying in vitro radiosensitivity, derived from tumors of varying radiocurability. Among the eight cell lines examined, three types of responses to fractionated irradiation were observed. In the group composed of tumor cell lines that were radioresistant in culture (D0 > 2 Gy) and derived from known local radiation failures or from tumor histologies associated with radiation failure, a gradual linear reduction in surviving fraction versus total dose was observed. In a second group, composed of cell lines that were radiosensitive in culture (D0 approximately 1 Gy) but derived from known radiation failures, the surviving fraction initially declined and began to plateau after 6 Gy (three fractions of 2 Gy). In the third group, composed of radiosensitive cell lines derived from tumors associated with high radiocurability, a rapid decline in surviving fraction versus total dose was observed. The in vitro response of human tumor cells to fractionated irradiation delivered at clinically relevant doses appears to be independent of in vitro X-ray sensitivity and p53 status but related to clinical radiocurability, suggesting a possible role in predicting tumor response to radiotherapy.