转化生长因子β1表达在小鼠放射性肺纤维化形成过程中的作用

目的探讨转化生长因子β１（ＴＧＦβ１）在小鼠放射性肺纤维化形成过程中表达变化及作用。方法雄性Ｃ５７ＢＬ小鼠,全肺１次照射１３Ｇｙ,不同时间取肺组织ＨＥ染色、Ｍａｓｏｎ染色、ＶＧ染色观察肺纤维化形成。逆转录聚合酶链反应（ＲＴＰＣＲ）方法测定肺组织内ＴＧＦβ１的表达。结果照射后８个月局部灶性纤维化形成。照射后３６小时ＴＧＦβ１表达下降;照射后２个月ＴＧＦβ１表达升高;至照射后８个月,略呈下降趋势,但仍高于正常对照。结论ＴＧＦβ１的表达在肺纤维化形成过程中起重要作用。     

慢性粒细胞白血病患者血小板膜糖蛋白Ⅳ再分布和胞内凝血酶敏感蛋白的释放

目的：探讨慢性粒细胞白血病（ＣＭＬ）患者血小板膜糖蛋白Ⅳ（ＧＰⅣ）再分布和胞内凝血酶敏感蛋白（ＴＳＰ）释放及血浆中β－血小板球蛋白（β－ＴＧ）和血小板第４因子（ＰＦ４）对其的影响作用。方法：应用１２５Ｉ分别标记血小板ＧＰⅠｂ、ＧＰⅡｂ／Ⅲａ、ＧＰⅣ和ＴＳＰ单克隆抗体并结合放射免疫法检测ＣＭＬ患者血小板膜上相应的结合位点，同时观察β－ＴＧ和ＰＦ４的抑制作用。结果：（１）ＣＭＬ患者未活化和诱导活化（凝血酶１Ｕ／ｍｌ）血小板膜ＧＰⅣ分布和再分布分别为３６０８０±１７０１０、４４３２０±３２３１０抗体结合分子数／血小板，明显高于相应对照组（Ｐ＜０．０１），而血小板膜ＧＰⅠｂ和ＧＰⅡｂ／Ⅲａ则无异常分布；（２）ＣＭＬ患者血小板胞内ＴＳＰ释放并未伴随血小板膜ＧＰⅣ再分布而发生相应的增多；（３）ＣＭＬ患者血浆中β－ＴＧ和ＰＦ４含量增高（Ｐ＜０．０５），体外实验发现β－ＴＧ和ＰＦ４明显地抑制血小板胞内ＴＳＰ释放。结论：ＣＭＬ患者血小板膜ＧＰⅣ再分布增多，可能成为判断血小板功能异常指标之一；而血小板胞内ＴＳＰ释放障碍或结合下降，则受血浆中β－ＴＧ和ＰＦ４的影响。     

VM26影响人肺腺癌细胞放射效应的机制探讨

目的：体外实验显示，ＶＭＤ６能提高人肺腺癌（ＳＰＣ）细胞放射效应。本文探讨其可能的作用机制。材料与方法：通过分段放射后克隆形成实验来研究ＶＭ２６对ＳＰＣ细胞放射损伤的修复；利用流式细胞技术（ＦＣＭ）观察不同作用时间及浓度下ＶＭ２６对ＳＰＣ细胞周期的影响。细胞存活曲线用单击多靶模式拟合。结果：ＶＭ２６（０．０６２５Ｍ）作用于细胞６小时，能使２Ｇｙ照射后，间隔６小时再组第二次剂量照射，得到的细胞存活曲线出现的“肩区”再现完全消失。当浓度升高到０．１２５Ｍ，放射引起的细胞杀灭明显增加。对ＳＰＣ细胞周期的影响，０．１２５Ｍ的ＶＭ２５作用２小时后，Ｇｏ／Ｇ１，期细胞比例升高，其阻滞率为４．２５％／小时。伴Ｇ２＋Ｍ期比例降低，ｓ期在作用１小时升高，然后恢复。在０．１２５－２．５Ｍ浓度范围内，ＶＭ２６作用于细胞１小时，细胞周期变化无明显差异。结论：ＶＭ２６能显著抑制ＳＰＣ细胞亚致死性损伤修复而对其细胞周期的影响未见５期和Ｇ２＋Ｍ期阻滞。     

不同化疗方案加放射治疗鼻咽癌的远期疗效

目的 探讨在鼻咽癌治疗中采用不同化疗方案配合常规放射治疗对肿瘤局部控制及远期生存的影响。方法 ３００例病理证实的鼻咽癌病例随机分为单纯放射治疗组１１４例，放射治疗＋新辅助化疗组９３例，放射治疗＋同步化疗组９３例。常规放射治疗：鼻咽原发灶ＤＴ７０Ｇｙ，颈部预防照射ＤＴ５０Ｇｙ，转移灶ＤＴ６５～７０Ｇｙ。新辅助化疗：氟尿嘧啶１０００ｍｇ／ｄ，３次／周，顺铂１００ｍｇ／周，交替各用２周，同步化疗：顺铂２０ｍｇ／ｄ，２次／周，氟尿嘧啶５００ｍｇ／ｄ，２次／周，交替各用３周。结果 ５年总生存率（ＯＳ）为５７．１％，５年无瘤生存率（ＤＦＳ）为５２．９％，５年无远地转移生存率（ＤＭＦ）为６１．０％，５年局部区域无复发生存率（ＬＲＦ）为８３．３％；各治疗组间５年ＯＳ、ＤＦＳ、ＤＭＦ和ＬＲＦ差异无显著性意义（Ｘ＾２值分别为２．９     

细胞色素P4501A1,2D6和谷胱甘肽硫转移酶基因多态性与肺癌易感性的研究

目的探讨细胞色素Ｐ４５０１Ａ１（ＣＹＰ１Ａ１），２Ｄ６（ＣＹＰ２Ｄ６）和谷胱甘肽硫转移酶（ＧＳＴＭ１）基因多态性与肺癌易感性的关系。方法用病例对照研究方法及ＰＣＲ┐ＲＦＬＰ等技术检测原发性肺癌和住院对照各５９例，分析ＣＹＰ１Ａ１基因ＭｓｐＩＣ型、ＣＹＰ２Ｄ６Ｃｈ型（Ｔ／Ｔ型）和ＧＳＴＭ１缺陷型〔ＧＳＴＭ１（－）〕三种纯合突变型频率分布及其交互作用。结果突变型在病例和对照组的频率分别为（ＣＹＰ１Ａ１ＭｓｐＩＣ型２５．４％、１５．３％（Ｐ＝０．１７），ＣＹＰ２Ｄ６ＣｈＴ／Ｔ型３５．６％，４７．５％（Ｐ＝０．２６），ＧＳＴＭ１（－）型５７．６％、４９．２％（Ｐ＝０．４６），无显著性差异。协同分析发现在男性中，１１．６％（５／４３）肺癌兼有ＭｓｐＩＣ型和ＧＳＴＭ１（－）型，对照组无１例（０／４３），Ｐ＝０．０３。结论结果提示在男性中ＣＹＰ１Ａ１ＭｓｐＩＣ型和ＧＳＴＭ１（－）型可能协同增加患肺癌的危险性。     

ＴＧＦ-β１与Ｓｍａｄ２基因在肝细胞肝癌中的表达及意义

目的：通过检测ＴＧＦ-β１和Ｓｍａｄ２基因在肝细胞肝癌（ＨＣＣ）中的表达,初步探讨ＴＧＦ-β／Ｓｍａｄ信号通路中激活型Ｓｍａｄ（Ｒ-Ｓｍａｄ）与ＨＣＣ的发生、发展之间的可能关系。方法：采用免疫组化ＡＢＣ法及原位杂交法（ＩＳＨ）检测４１例ＨＣＣ组织及癌旁组织ＴＧＦ-β１、Ｓｍａｄ２蛋白、Ｓｍａｄ２ｍＲＮＡ的表达,５例外伤性肝破裂手术切除标本作正常对照,比较正常对照、癌组织、癌旁组织中上述三者表达的差异,并进行图像分析和统计学分析。结果：正常对照组ＴＧＦ-β１、Ｓｍａｄ２蛋白、Ｓｍａｄ２ｍＲＮＡ均呈阴性表达。ＴＧＦ-β１在ＨＣＣ组织中阳性表达率为７５.６％（３１／４１）,在癌旁组织中为９５.１％（３９／４１）,二者比较差异显著（Ｐ＜０.０５）;Ｓｍａｄ２蛋白在ＨＣＣ组织中阳性表达率为４３.９％（１８／４１）,在癌旁组织中为５６.１％（２３／４１）,二者比较无显著差异（Ｐ＞０.０５）;Ｓｍａｄ２ｍＲＮＡ在ＨＣＣ组织中阳性表达率为６１.０％（２５／４１）,在癌旁组织中为８２.９％（３４／４１）,二者比较有显著差异（Ｐ＜０.０５）。ＨＣＣ组织中ＴＧＦ-β１、Ｓｍａｄ２蛋白、Ｓｍａｄ２ｍＲＮＡ的表达与病理分级均无显著相关性（Ｐ＞０.０５）。癌旁组织中Ｓｍａｄ２蛋白的阳性面积百分比、吸光值及Ｓｍａｄ２ｍＲＮＡ的阳性面积百分比均显著高于ＨＣＣ组织（Ｐ＜０.０５）。结论：ＴＧＦ-β１和Ｓｍａｄ２基因过表达可能在ＨＣＣ的发生、发展中发挥作用。     

连续加速超切割与后程加速超分割治疗食管癌

目的 比较连续加速超分割（ＣＡＨＦ）和后程加速超分割（ＬＣＡＦ）放射治疗食管癌的疗效和毒性。方法 １０１例食管鳞癌患者前瞻性随机分成２个组。ＬＣＡＦ组（５２例）前２／３疗程为常规分割（５次／周,１．８Ｇｙ／次）,照射４１．４Ｇｙ后缩野改加速超分割（２次／ｄ,１．５Ｇｙ／次）照射２７Ｇｙ,总量６８．４Ｇｙ,４１次,４４～４６ｄ,ＣＡＨＦ组（４９例）从治疗开始,２次／ｄ,１．５Ｇｙ／次,照射至３９Ｇｙ     

表皮生长因子受体单克隆抗体抗肺癌作用的研究

目的 实验观察表皮生长因子受体单克隆抗体（ＥＧＦＲ ＭcＡb）egf／r３对肺癌的治疗 作用。方法 体外细胞增殖抑制实验采用ＭＴＴ法,裸鼠体内移植瘤采用同时治疗（Ｔ１组）与一治疗（Ｔ２组）两种方案。结果 egf／r３ＭcＡb对高表达ＥＧＦＲ的ＳＰＣ－Ａ１和Ａ５４９肺癌细胞体外均具有增殖抑制作用,并呈剂量依赖性;以ＳＰＣ－Ａ１进行裸鼠皮下移植体内实验,至治疗结束,Ｔ１组与５０％成瘤（３/６）,对照组１００％成瘤（     

半边旗抗肿瘤有效成分6F对HL-60细胞周期的影响及体外增效作用

目的：研究半边旗抗肿瘤有效成分６Ｆ对ＨＬ－６０细胞周期的影响及对常用抗肿瘤药的体外增效作用。方法：应用流式细胞光度术（ＦＣＭ）测定细胞周期，应用噻唑蓝（ＭＴＴ）法测定药物对细胞的抑制率。结果：不同浓度６Ｆ作用６小时即可使ＨＬ－６０细胞Ｓ期及Ｇ２／Ｍ期比例升高，Ｇ１期比例下降，并呈一定的剂量效应关系，当作用到２４小时后，Ｓ期比例进一步升高，但Ｇ２／Ｍ期比例稍有回落。低浓度６Ｆ分别与２－氯代脱氧腺苷（２－ＣＬｄＡｄｏ），顺铂（ＣＤＤＰ），长春新碱（ＶＣＲ），氟尿嘧啶（５ＦＵ）合用可增强它们对ＨＬ－６０细胞的杀伤作用，ｑ值大于０．８５，与各药有相加或协同作用，６Ｆ对２－ＣｌｄＡｄｏ，ＣＤＤＰ，ＶＣＲ，５ＦＵ的增效倍数分别为１．５８，１．５３，１．５５，１．３８。结论：６Ｆ可明显阻断ＨＬ－６０细胞在Ｓ期及Ｇ２／Ｍ期；６Ｆ可增强上述药物对ＨＬ－６０细胞的杀伤作用。已知，２－ＣｌｄＡｄｏ阻断细胞在Ｓ期，ＣＤＤＰ和ＶＣＲ阻断Ｇ２／Ｍ期，５ＦＵ阻断Ｇ１期。鉴于所试药物对细胞周期的影响不同，提示６Ｆ的体外增效作用可能与此有关。     

单剂量黄曲霉毒素B1致大鼠肝癌作用的短期实验模型

本文报告单剂量黄曲霉毒素Ｂ１（ＡＦＢ１）致大鼠肝癌作用短期实验模型的研究。６周龄、雄性Ｗｉｓｔａｒ大鼠，经腹腔一次性注射不同剂量（０、０．５０、０．７５、１．００和１．５０ｍｇ／ｋｇ体重）的ＡＦＢ１，作为启动剂，两周后，饲以含０．０１５％的２－乙酰氨基芴（２－ＡＡＦ）饲料４周，实验第三周末，施行肝大部分切除术（ＰＨ）。所有动物于实验第６周处死，取肝组织作Ｇａｍｍａ－谷氨酰转肽酶（ＧＧＴ）化学染色，     

DNA repair and cell repair: Are they related?

Evidence of damage-repair processes is reviewed in connection with 3 types of cytotoxic cell treatments: X-radiation; far-ultraviolet (UV) (254 nm) light; and fluorescent light (FL) exposure of cells that had been grown in the presence of 5-bromodeoxyuridine (BUdR). In each case, the processes are characterized relative to cell survival and loss of DNA integrity, i.e. the presence of single-strand breaks evident under alkaline conditions and dimers containing thymine. From quantitative data of the induction of both types of end points, the number of DNA lesions are compared that are produced by a Do dose; that is, a dose that reduces survival by the factor $\text{1}\text{e}$ (= 0.37). The number of single-strand breaks for the treatments BUdR/FL, X-rays, and far-UV are, respectively ～50,000, ～1,000, and ～100. From such data, and upper-limit estimates of the persistence of breaks in X-irradiated surviving cells, it is concluded that: (1) X-ray survivors repair a large number of DNA lesions; and (2) X-ray lethality results from damage registered in a small fraction of the genome and/or the misrepair of supernumerary DNA lesions.     

DNA repair and repair diseases: between molecular models and clinical reality

To study the biological mechanisms of the repair of the radiation-induced DNA damage leads to two major medical applications: (1) the identification of the radiosensitive patients by using appropriate predictive assays in order to avoid toxicity due to radiation therapy and sometimes to chemotherapy; (2) the decrease of the radioresistance of tumour cells to obtain a better local control. To transpose fundamental biological knowledge from experimental in vitro clinic is delicate and sometimes too hasty, though necessary. In mechanistic terms, clinical features are once again a very rich and under-exploited approach to identify the molecular mechanisms of the DNA repair function. An exhaustive survey of the clinical cases of radiosensitivity with biological samples and with long course surveillance is an inverse approach, probably promising but still difficult to apply. Unlike classical reviews, this article attempts to identify the major genetic syndromes associated with radiosensitivity and cancer predisposition in order to deduce the different stages of major mechanisms of DNA double-strand breaks repair. Emphasis is placed on the importance of studying this repair at the functional level. Surprisingly, among the genetic syndromes associated to radiosensitivity there are some anomalies, not linked to DNA repair itself but to the intracellular trafficking. The repair function but therefore also the signalling are then logically therapeutic targets applicable in radiotherapy but with a very accurate ballistic sparing of the healthy tissues.     

DNA的损伤与修复

细胞的生物信息储存在DNA中。在真核细胞中,绝大多数（98％）DNA与蛋白质结合形成染色质存在于细胞核内,一小部分存在于其他细胞器中,如线粒体内。DNA由鸟嘌呤、腺嘌呤、胸腺嘧啶、胞嘧啶、戊糖和磷酸组成,碱基不同的排列顺序编码了不同的生物信息。在细胞的生存过程中,DNA会遭到内源性和外源性的损伤（表1）,例如放射线和化学物质。正常细胞的DNA损伤是诱发疾病的原     

经碱基切除修复的氧化性DNA损伤与肝癌的发生

在生物体内如果过氧化物的产生和消除存在不平衡均会导致氧化应激的发生．很多病理生理状况跟氧化应激有密切的关系。氧化应激产生的活性氧．可诱发DNA碱基发生化学修饰，在嘌呤残基的C-8位置和DNA整合，形成8-羟基二羟鸟嘌呤并进-步氧化形成8-羟基鸟嘌呤（8-OHdG）。8-OHdG是一种主要的DNA氧化损伤产物，经碱基切除修复通路来完成修复，若不及时修复，则参与癌变的发生。     

DNA damage repair and genetic polymorphisms: assessment of individual sensitivity and repair capacity

PURPOSE: To study the repair capacity after X-ray irradiation in human peripheral blood cells of healthy subjects, in relation to their genotypes. METHODS AND MATERIALS: The peripheral blood of 50 healthy subjects was irradiated in vitro with 2 Gy of X rays and the induced DNA damage was measured by Comet assay immediately after irradiation. DNA repair was detected by analyzing the cells at defined time intervals after the exposure. Furthermore, all subjects were genotyped for XRCC1, OGG1, and XPC genes. RESULTS: After X-ray irradiation, persons bearing XRCC1 homozygous variant (codon 399) genotype exhibited significantly lower Tail DNA values than those bearing wild-type and heterozygous genotypes. These results are also confirmed at 30 and 60 min after irradiation. Furthermore, XPC heterozygous subjects (variant codon 939) showed lower residual DNA damage 60 min after irradiation compared with wild-type and homozygous genotypes. CONCLUSION: The results of the present study show that polymorphisms in DNA repair genes could influence individual DNA repair capacity.     

Drug resistance and DNA repair

Summary DNA repair confers resistance to anticancer drugs which kill cells by reacting with DNA. A review of our current information on the topic will be presented here. Our understanding of the molecular biology of repair of 0⁶-alkylguanine adducts in DNA has advanced as a result of the molecular cloning of the E. coli ada gene but the precise role of this lesion in the cytotoxic effects of alkylating agents in mammalian cells is not completely understood. Less progress has been made in understanding the enzymology and molecular biology of DNA cross-link repair even though such lesions are important for the cytotoxic effects of the widely used bifunctional alkylating agents and platinum compounds. It is evident that drug sensitive or resistant phenotypes are as highly complex as are the effects of DNA damage on cell metabolism and various aspects of these effects are discussed. Few clear correlations have been made between quantitative differences in DNA repair capacity and cellular sensitivity but assays which were developed to measure fidelity and intragenomic heterogeneity in DNA repair are beginning to be applied. Such studies may reveal subtle differences between sensitive and resistant cell lines. The molecular cloning of human DNA repair genes by transfection into drug sensitive rodent cells has been attempted. Some success has been achieved in this area but the functions of the cloned genes have yet to be identified.     

Base excision repair and cancer

Base excision repair is the system used from bacteria to man to remove the tens of thousands of endogenous DNA damages produced daily in each human cell. Base excision repair is required for normal mammalian development and defects have been associated with neurological disorders and cancer. In this paper we provide an overview of short patch base excision repair in humans and summarize current knowledge of defects in base excision repair in mouse models and functional studies on short patch base excision repair germ line polymorphisms and their relationship to cancer. The biallelic germ line mutations that result in MUTYH-associated colon cancer are also discussed.