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用PCR-SSCP分析法对36例矽肺患者的石蜡包埋的原发性肺癌组织p53基因第5、7、8外显子进行了检测,检出突变15例。突变在第5、7、8外显子上都有发生,但以第8外显子上发现的阳性突变最多。对肿瘤类型和p53基因突变的关系进行了分析,发现矽肺病例肺腺癌p53基因阳性突变率最高,为53.9%,高于普通型肺癌(33.0%)。进一步对其中1例样本进行核苷酸序列直接测定,结果显示第5外显子非突变热点区的第144位密码子核苷酸由CAG突变为AAG,氨基酸由谷氨酰胺突变为赖氨酸,以上结果与非职业肺癌明显不同,提示p53基因突变在矽肺病例肺癌发生中起着重要作用,可能与矽尘作业环境中含有的某些化学致癌物有关。 相似文献
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石英的人类致癌性在DNA分子水平的证据 总被引:10,自引:3,他引:10
收集36例石英粉尘作业工人肺癌(石英肺癌)的组织石蜡包埋物,提取其 D N A,对 p53基因和 K ras 基因进行了 P C R S S C P、 P C R R F L P及 D N A 测序分析,发现具有完全有别于普通肺癌的特异基因突变谱。小细胞肺癌的 p53基因突变多发于第8外显子,腺癌的 p53基因突变率高。石英肺癌的 K ras 基因突变未见一例发生于普通肺癌突变热点区第12密码子上,相反发现多处非热点区突变,突变类型以 G→ C 突变为主。 相似文献
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接触矽尘及电焊烟尘工人肺癌组织中p53基因的初步研究 总被引:8,自引:0,他引:8
为了从分子水平揭示矽尘与肺癌的关系,采用免疫组化和PCR-SSCP法对36例矽尘相关肺癌和6例电焊烟尘相关肺癌的抑癌基因p53的突变进行了研究。样品为石蜡包埋的肺肿瘤组织块,平均保存13.4年。PCR-SSCP分析显示,18例病例中存在异常的电泳条带(20处突变),占所测42个样品的42.9%,其中50%的突变发生于第8外显子上(10/20)。以上发现有别于非职业性肺癌的基因突变谱。在非职业性肺癌中,第8外显子的突变频率介于17.5%~23.5%。尘肺相关肺癌基因突变的发生频率,在不同病理分类的肺癌中也与普通肺癌不同。在普通肺癌中,小细胞肺癌p53基因突变率最高(70%),肺腺癌最低,为33%。而本研究结果相反,肺腺癌最高,小细胞肺癌为最低,分别为53.9%和30.8%。免疫组织化学观察也显示了很高的p53突变体蛋白表达的发生率(46.9%)。本研究仅做两例测序分析,意外地发现,探测到的两处点突变均发生于p53基因突变的非热点区,而且均发生于第144密码子上。基因突变谱的不同,显示矽尘、电焊烟尘中可能具有特异的致癌物和致癌机理。 相似文献
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石棉肺癌组织中p53基因突变的PCR-SSCP及部分序列分析研究 总被引:1,自引:0,他引:1
为研究石棉致癌的分子机理,本研究首次直接分析石蜡包埋的石棉肺癌病例肺组织中抗癌基因p53的突变情况。利用聚合酶链反应-单链构象多态性(PCR-SSCP)技术分析10例石棉肺癌病例,检测到7例(8个片段)存在p53基因的突变,突变位点位于其第5、7和8外显子区内,突变率为70%。对其中2例进行PCR产物直接序列分析,发现其基因一级结构分别发生C→A和T→A转换。 相似文献
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利用化学致突变物甲基丙烯酸环氧丙酯体外诱导人胚肺成纤维细胞,使之发生转化,分离转化细胞克隆。经PCR特异性扩增p53基因外显子第5和第8,银染单链构象多态性(SSCP)分析,结果表明转化细胞中p53基因外显子第8发生突变,揭示出p53基因在化学致突变物诱导细胞转化中起着重要作用。 相似文献
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肺癌中p53基因突变类型和可能致癌因素分析 总被引:5,自引:0,他引:5
为了研究肺癌中p53基因的作用及突变类型与不同致癌物的可能关系,用PCR-SSCP核酸序列技术分析了原发非小细胞肺癌中p53基因的突变谱,结果发现128例中94例发生突变,其中86例为点突变,7例为缺失和插入突变,1例为拼接部位突变。点突变以G→T和T→G突变为主(63.9%),G→A和A→G占25.6%,这些结果提示p53基因突变与非小细胞肺癌发生有密切关系,并根据其突变特点分析了可能的环境致癌物。 相似文献
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Carton T Tan XD Hartemann P Joyeux M 《International journal of hygiene and environmental health》2007,210(1):69-77
CGT>CTT transversion in codon 273 of the P53 tumor-suppressor gene is one of the major mutations detected in human tumors. Within an epidemiological framework, we investigated the use of a genotypic selection method to measure this point mutation. The allele-specific polymerase chain reaction (AS-PCR) that was developed was able to detect 10 mutant copies of the gene among a total of 5 x 10(5) wild-type copies. We used this assay to detect CGT>CTT transversions in buccal cell DNA of production workers (n=76) from a viscose factory exposed to carbon disulfide (amongst other pollutants) and in the DNA of non-exposed office workers (n=67). The mutation appeared more frequently in the exposed than in the non-exposed worker who were smokers. The results of the study indicate that occupational exposure results in a significant increase in P53 CGT>CTT transversions and more especially identified occupational exposure in combination with smoking as a significant risk factor for the mutation. We conclude that AS-PCR of the P53 273rd codon transversions is a suitable technique for studying the effects of occupational exposure. 相似文献
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目的探讨p53基因突变与人乳头状肉瘤病毒16(HPV16)感染在食管癌发病中的作用及相互关系。方法应用病例-病例研究方法进行分析,采用聚合酶链反应(PCR)、单链构像多态性(SSCP)、测序等分子生物学技术对110例食管癌组织标本中p53基因的突变与HPV16感染进行了检测。结果110例食管癌组织标本p53基因突变率为49.1%,其中外显exon5—6,exon7,exon8—9的突变率分别为19.1%,27.3%,17.2%。食管癌组织HPV16的检出率为49.1%。吸烟患者p53基因突变率(61.4%)明显高于非吸烟患者p53基因突变率(48.2%),差异有统计学意义;淋巴结转移患者p53基因突变率(65.2%)明显高于无淋巴结转移患者p53基因突变率(37.5%);HPV16阳性者中,p53突变率是40.7%,HPV16阴性者仅为57.1%,两者差异无统计学意义。结论HPV16感染可能是食管癌高发区的危险因素;p53基因突变与吸烟、淋巴结转移有明显相关性;HPV16感染和p53基因突变可能是2个独立的事件。 相似文献
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为了利用石蜡包埋的病理组织来研究石棉肺癌的基因突变情况,选用10例石蜡包埋的石棉肺癌组织进行PCR-SSCP分析,检测其抗癌基因p53的第5、第7和第8外显子的突变情况。经银染检查,发现4个病例的p53基因的第7或第8外显子片段呈突变阳性。用放射性自显影的PCR-SS-CP方法分析这10例病例,检测到7个病例的p53基因第7或第8外显子片段呈突变阳性。用两种方法检测均未发现这10个病例的第5外显子呈突变阳性。银染PCR-SSCP检测可检出放射性自显影PCR-SSCP分析结果的60%,二者的结果相符合。因而,简便、灵敏而且危害性小的银染检测方法,可以代替放射性自显影用于PCR-SSCP分析,研究石棉肺癌的基因突变情况。 相似文献
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P53 mutations in hepatocellular carcinoma patients in Egypt 总被引:3,自引:0,他引:3
El-Kafrawy SA Abdel-Hamid M El-Daly M Nada O Ismail A Ezzat S Abdel-Latif S Abdel-Hamid A Shields PG Loffredo C 《International journal of hygiene and environmental health》2005,208(4):263-270
The p53 gene plays a major role in hepatocellular carcinoma (HCC). Acquired mutations may provide clues to etiology, as some carcinogenic agents are associated with specific genetic changes in p53. Our aim was to analyze the spectrum of p53 mutations in tumor tissues from subjects with HCC in Egypt, where there is a rising incidence of HCC due to hepatitis C virus (HCV). We collected tumor tissues from 41 subjects with HCC diagnosed at the National Cancer Institute of Cairo University during 2000-2003. Sequence mutations were analyzed by the Affymetrix GeneChip technique. HCV RNA was detected in the sera of 37 subjects (90%). Only one patient had a current HBV infection. A total of 17 of the 41 subjects (41%) had p53 mutations. Thirteen of these were in exon 7, of which 10 were in codon 249, but only 8 of the 10 were the R249S mutation, previously reported to be associated with aflatoxin exposure. The other three exon 7 mutations were found in codons 232, 242 and 248. A total of three mutations were detected in exon 5 codons 133, 144 and 176. One mutation was detected in exon 8 codon 275. Unlike previous studies, this population is characterized by a high prevalence of chronic HCV infection. The presence of the R249S mutation in exon 7 may indicate that these subjects with HCC have been exposed to aflatoxin (AFB1), and further investigation is in progress to measure AFB1-albumin adducts in the sera of these subjects. 相似文献
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In our previous study, we found no genetic alteration in exons 1 and 2 of Ha- and Ki-ras oncogenes nor in exons 5 to 9 of the p53 suppressor gene in seven Japanese malignant mesothelioma patients exposed to asbestos. To examine further whether malignant mesothelioma due to asbestos has genetic alterations in the p53 suppressor gene and in Ha- and Ki-ras oncogenes, we analyzed point mutations of these genes in paraffin embedded operative open biopsied samples of the primary tumor of malignant mesothelioma in twelve American patients. The genetic analysis was conducted by the PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) method in all patients and by sequencing analysis of DNA bases in the two patients with suspected gene mutation. The analysis of the p53 suppressor gene showed an amino acid converting mutation of exon 7 in one patient and a polymorphism of exon 6 in another patient; the former patient was a heavy smoker with a biphasic cell type. No genetic alteration was found in exons 1 and 2 of Ha- and Ki-ras oncogenes in any of the patients. The results suggest that the effects of asbestos on the p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma are negligible. Further studies are needed to examine whether the observed mutation of the p53 suppressor gene is due to the combined effects of asbestos and smoking or to other unknown factors. 相似文献
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目的 分析不同地区食管癌组织中 p5 3基因第 5外显子的突变谱。 方法 采用PCR扩增产物纯化后直接DNA序列测定技术对陕西省西安市 4 2例和河南省林州市 4 3例食管癌标本 p5 3基因第 5外显子突变情况进行检测。结果 西安和林州市食管癌标本中 p5 3基因第 5外显子突变率分别为 14 3% (6 /42 )和 18 6 % (9/43) ,两地突变率比较差异无统计学意义 (P >0 0 5 )。西安 6个突变位点中 4个为点突变 ,2个为缺失突变 ;林州 10个突变位点中9个为点突变 ,1个为插入突变。西安市有 4例突变发生在 12 6~ 12 8位点 ,林州市仅有 2例发生在该区域 (2 /10 ) ,但两者相比差异无统计学意义 (P >0 0 5 )。结论 西安市食管癌 p5 3基因第 5外显子的突变位点相对集中 ,林州市突变位点比较分散 ,可能与该地区多种危险因素的暴露有关。 相似文献
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Wei Mo Wanglei Xu Min Hong Tingyi Yang Yuhong Shi Yang Jiao Jihua Nie Fengmei Cui Jianping Cao Shuyu Zhang 《Journal of radiation research》2022,63(5):706
Radon is a naturally occurring radioactive gas and considered as a serious carcinogen to humans. Continuous radioactive decay of this gas emits high-energy alpha particles. Long-term radon exposure induces oxidative stress and inflammatory response, which results in chronic lung diseases. However, biological effects after radon exposure in other organs have been rarely reported. As the outermost organ of the human body, the skin suffers from environmental damage to agents such as air pollution. Epidemiological studies indicated that areas with high level of radon had a high incidence of skin cancer. However, whether radon exposure induces skin damage has not been reported yet. In this study, we established a radon-exposed mouse model and found that radon exposure affected the structure of skin tissues, which was manifested by inflammatory cell infiltration and skin atrophy. Using proteomic approach, we found 45 preferentially expressed proteins in 60 Working Level Months (WLM) group and 314 preferentially expressed proteins in 120 WLM group from radon-exposed skin tissues. Through microRNA (miRNA) sequencing profiling analysis, 57 dysregulated miRNAs were screened between the control and radon-treated mouse skin. By integrating the dysregulated proteins and miRNAs, radon-induced fatty acid synthase (FASN) was investigated in greater detail. Results showed that FASN was regulated by miR-206-3p and miR-378a-3p and involved in the pathogenesis of radon-induced skin damage. Overexpression of FASN inhibited the proliferation, and induced in WS1 cells. Our present findings illustrate the molecular change during radon-induced skin damage and the potential role of FASN during this process. 相似文献
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An economic evaluation of a radon-induced lung cancer prevention programme for schools in the United Kingdom is undertaken in this study, which presents a cost-effectiveness analysis with a generalisable model for estimating the cost-effectiveness of a radon remediation programme for schools from a societal perspective. It follows the guidelines for the methodological framework now considered appropriate in the economic evaluation of health interventions and employs best available national UK data and information from Northamptonshire on the costs and effectiveness of radon identification and remediation in schools, and the costs and health impact of lung cancer cases for all state schools in Northamptonshire between 1993 and 1997 (348 schools, including 170 adult staff and 1820 pupils). The resultant cost-effectiveness ratio was 7550 per life-year gained in 1997 UK pound sterling. Results from the sensitivity analysis show that the ratio is particularly sensitive to assumptions concerning two parameters: the average capital cost of remediation and discount rate applied to life years. This study highlights the need for the evaluation of other schools remediation-based radon-induced lung cancer prevention programmes in other countries using similar methodological techniques. Compared to other health interventions in the UK, the schools programme has a favourable ratio. When compared to other lung cancer prevention programmes available, however, the schools programme ratio is less favourable. Uncertainties remain around increased risks from childhood exposure to indoor radon. 相似文献
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目的 观察氯化镉(CdCl2)诱发人支气管上皮(16HBE)细胞系恶性转化过程中human MutS homologue 2(hMSH2)基因mRNA和蛋白动态变化的规律及其序列突变情况,进一步探讨CdCl2的致癌机制.方法 用反转录-聚合酶链反应(PT-PCR)和免疫组织化学(SP)法检测16HBE细胞、CdCl2恶性转化16HBE细胞系不同阶段(第5、15、35代细胞及成瘤细胞)hMSH2基因mRNA和蛋白的表达情况;并测序分析hMSH2基因第6、7、8、9、12外显子的序列情况.结果 随着转化代数的增加,hMSH2基因mRNA和蛋白的表达水平逐渐降低,到第35代细胞后表达明显下降,差异有统计学意义(P<0.01).hMSH2基因第8外显子在第1、2、7位点上均出现胸腺嘧啶T缺失,第9外显子在第20、182位点出现腺嘌呤A缺失,第12外显子在241位点上出现腺嘌呤A插入,所有的突变均为移码突变.结论 CdCl2的分子致癌机制可能与hMSH2基因的下调和突变有关. 相似文献
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目的 分析云南省结核分枝杆菌利福平耐药基因rpoB突变特征。方法 应用聚合酶链式反应(polymerase chain reaction,PCR)法对1株H37Rv结核分枝杆菌标准株及102株结核分枝杆菌临床分离株中包含"利福平耐药决定区"在内的rpoB基因片段进行扩增,并将扩增产物进行直接基因测序,测序结果用MEGA 5软件进行分析。结果 利福平耐药基因型与表型的符合率为92.00%(69/75),突变类型11种,涉及氨基酸11种,均为碱基的点突变,单位点突变占92.96%,联合突变占7.04%,突变率最高的位点依次是rpoB531(43.66%)、rpoB526(26.76%)、rpoB516(9.86%),前3个位点的突变占总突变的80.28%。初复治患者临床分离株rpoB耐药突变位点构成差异无统计学意义((口恶)2=7.653,P=0.354);耐多药结核与单耐利福平临床分离株rpoB突变位点构成差异有统计学意义((口恶)2=16.917,P=0.010)。结论 对rpoB的突变的检测在云南省可作为利福平耐药筛查的重要指标。rpoB基因突变可能不受是否使用过利福平和使用时间长短的影响,但是异烟肼可能会影响结核分枝杆菌rpoB基因突变的分子机制。 相似文献
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某铀矿工人痰细胞中p16和MGMT基因的甲基化状态 总被引:1,自引:0,他引:1
目的检测某铀矿氡职业暴露人群痰细胞中6-氧-甲基嘌呤-DNA甲基转移酶(MGMT)基因和p16基因的甲基化状态,为寻找氡致肺癌高危人群的分子标记物提供试验依据。方法91名氡职业暴露工人按氡子体累积暴露剂培工作水平月(WLM)分为高(〉120WLM)、中(60~120WIN)、低(30~60WLM)和较低(2~30WLM)4个剂量组,用聚合酶链反应-甲基化特异性(MSP)检测4组人群痰细胞中的p16和MGMT基因的异常甲基化状态。结果随着氡子体累积暴露剂量的增加,p16基因甲基化率(0.00%,20.00%)、MGMT基因甲基化率(0.00%~28.00%)、总甲基化率(0.00%~40.00%)均呈明昆上升趋势,差异有统计学意义(P〈0.01)。结论p16和MGMT基因甲基化与氡子体累积暴露剂量有关。 相似文献