焦炉工外周血淋巴细胞热应激蛋白90、60及27的表达与细胞损伤的关系
|
摘要
目的探讨焦炉工外周血淋巴细胞热应激蛋白90、60及27(HSP90、HSP60和HSP27)的表达水平及其与外周血细胞损伤之间的关系及意义。
方法选取某钢铁集团公司某焦化厂焦炉作业工人288名作为暴露组,根据作业环境监测结果和工作地点分为高剂量组172人,低剂量组116人;同时选取该焦化厂2km外、无有毒作业接触史的某医院医护人员和管理人员38名作为对照组。调查其一般情况、工作史、个人史等情况;对作业环境进行监测;同时取受试者的肘静脉血,应用Western blot法测定外周血淋巴细胞的HSP90、HSP60和HSP27水平;用ELISA试剂盒测定外周血清乳酸脱氢酶(LDH)活力和丙二醛(MDA)含量;用单细胞凝胶电泳法(SCGE,即彗星试验)测定外周血淋巴细胞DNA的损伤程度。
结果各组调查对象在年龄、性别、吸烟、饮酒方面差异均无显著性(P＞0.05)。热应激蛋白表达结果显示,焦炉工高剂量组淋巴细胞HSP90水平(比值)(0.24±0.32)高于低剂量组(0.12±0.30)和对照组(0.06±0.33),具有统计学差异(P＜0.05);HSP60、HSP27各组之间未见统计学差异。LDH测定结果显示,焦炉工高剂量组血清LDH水平(246.7±42.79)U/L高于低剂量组(205.7+33.72)U/L和对照组(199.7±31.78)U/L,具有统计学差异(P＜0.05)。MDA测定结果也显示,焦炉工高剂量组血清MDA水平(2.68±0.67)nmol/ml高于低剂量组(2.35±0.58)nmol/ml和对照组(2.24±0.66)nmol/ml,具有统计学差异(P＜0.05)。彗星试验的各项结果显示,焦炉工人外周血淋巴细胞DNA损伤显著高于对照组,且高剂量组工人(炉顶、炉侧)的DNA损伤显著高于低剂量组的工人(炉底及辅助工)(P＜0.05)。经线性趋势x~2分析(x~2值为36.411,P＜0.001)和Spearman相关分析(r=-0.345,P＜0.001),随多环芳烃(PAHs)暴露水平的增高,DNA损伤程度也呈逐渐加重(即损伤级别增高)的趋势。经多元回归分析,彗星实验的Olive尾矩与焦炉工人的PAHs接触剂量存在着剂量—反应关系。(β=-0.117,P=0.030)
结论1、淋巴细胞彗星试验结果显示,焦炉逸散物可导致遗传物质损伤。2、焦炉工外周血淋巴细胞HSP90等HSPs水平的增高可能起到保护细胞DNA免受致癌物PAHs损伤作用。3、焦炉工人血清中的LDH和MDA及外周血淋巴细胞中的HSP90可为PAHs暴露的生物标志物的研究提供科学依据。
Objective To explore the relationship between the expression of heat shock protein 90,60 and 27(HSP90,HSP60 and HSP27)and cell damage in peripheral blood of workers exposed to coke oven emissions.
Methods 288 coke oven workers in X steel factory were divided into high dose group and low dose group on the basis of environment monitoring result and work place.There were 172 men in high dose group and 116 men in low dose group.While 38 workers unexposed occupationally carcinogenic substances were selected as the control group,who were employed in medical therapy unit nearby 2 kilometers from steel factory.We investigated their general information,history of personal and occupational exposure,and the work environment.Blood samples were collected immediately after a shift at the end of a working day from 288 coke oven workers and 38 control workers.Levels of HSP90,HSP60 and HSP27 in peripheral blood lymphocytes were measured by Western blot.LDH and MDA were measured by ELISA. Chromosomal aberrations and the degree of DNA damage in peripheral blood lymphocytes were detected by comet assay.
Results There were no significant differences among those groups regarding age,sex, smoking and drinking habits(P＞0.05).Levels of HSP90(ratio)in peripheral blood lymphocytes in three groups were separately 0.24±0.32,0.12±0.30 and 0.06±0.33.They increased significantly compared with that of the control.But levels of HSP60 and HSP27 were not significantly different among those groups.Monitoring result of LDH appeared that the level of LDH in the high dose group((246.7±42.79)U/L)was higher than those in the low dose group ((205.7±33.72)U/L)and in the control group((199.7±31.78)U/L)(P＜0.05).Detectable result of MDA presented that the level of MDA in the high dose group((2.68±0.67)nmol/ml)was bigger than those in the low dose group((2.35±0.58)nmol/ml)and in the control group ((2.24±0.66)nmol/ml)(P＜0.05).Compared with the control group,there was significant difference in tail length,Olive Tail Moment of occupational exposure workers,high dose group＞low dose group＞control group(P＜0.05).The degree of DNA damage increased with the rising of exposure BaP dose(χ~2=36.411,P＜0.001;Spearman r=-0.345,P＜0.001).There is a dose-effect relationship between Olive and exposed dose of PAHs.(β=-0.117,P=0.030)
Conclusion 1.Result of comet assay showed that Coke oven emission could result in genetic damage.2.The increase of HSP90 level may be involved in protection of DNA from genotoxic damage induced by carcinogen.3.LDH and MDA in peripheral blood and HSP90 in peripheral blood of coke oven workers could offer scientific evidence for the study of an exposure biomarker to evaluate PAHs contact level.
方法选取某钢铁集团公司某焦化厂焦炉作业工人288名作为暴露组,根据作业环境监测结果和工作地点分为高剂量组172人,低剂量组116人;同时选取该焦化厂2km外、无有毒作业接触史的某医院医护人员和管理人员38名作为对照组。调查其一般情况、工作史、个人史等情况;对作业环境进行监测;同时取受试者的肘静脉血,应用Western blot法测定外周血淋巴细胞的HSP90、HSP60和HSP27水平;用ELISA试剂盒测定外周血清乳酸脱氢酶(LDH)活力和丙二醛(MDA)含量;用单细胞凝胶电泳法(SCGE,即彗星试验)测定外周血淋巴细胞DNA的损伤程度。
结果各组调查对象在年龄、性别、吸烟、饮酒方面差异均无显著性(P＞0.05)。热应激蛋白表达结果显示,焦炉工高剂量组淋巴细胞HSP90水平(比值)(0.24±0.32)高于低剂量组(0.12±0.30)和对照组(0.06±0.33),具有统计学差异(P＜0.05);HSP60、HSP27各组之间未见统计学差异。LDH测定结果显示,焦炉工高剂量组血清LDH水平(246.7±42.79)U/L高于低剂量组(205.7+33.72)U/L和对照组(199.7±31.78)U/L,具有统计学差异(P＜0.05)。MDA测定结果也显示,焦炉工高剂量组血清MDA水平(2.68±0.67)nmol/ml高于低剂量组(2.35±0.58)nmol/ml和对照组(2.24±0.66)nmol/ml,具有统计学差异(P＜0.05)。彗星试验的各项结果显示,焦炉工人外周血淋巴细胞DNA损伤显著高于对照组,且高剂量组工人(炉顶、炉侧)的DNA损伤显著高于低剂量组的工人(炉底及辅助工)(P＜0.05)。经线性趋势x~2分析(x~2值为36.411,P＜0.001)和Spearman相关分析(r=-0.345,P＜0.001),随多环芳烃(PAHs)暴露水平的增高,DNA损伤程度也呈逐渐加重(即损伤级别增高)的趋势。经多元回归分析,彗星实验的Olive尾矩与焦炉工人的PAHs接触剂量存在着剂量—反应关系。(β=-0.117,P=0.030)
结论1、淋巴细胞彗星试验结果显示,焦炉逸散物可导致遗传物质损伤。2、焦炉工外周血淋巴细胞HSP90等HSPs水平的增高可能起到保护细胞DNA免受致癌物PAHs损伤作用。3、焦炉工人血清中的LDH和MDA及外周血淋巴细胞中的HSP90可为PAHs暴露的生物标志物的研究提供科学依据。
Objective To explore the relationship between the expression of heat shock protein 90,60 and 27(HSP90,HSP60 and HSP27)and cell damage in peripheral blood of workers exposed to coke oven emissions.
Methods 288 coke oven workers in X steel factory were divided into high dose group and low dose group on the basis of environment monitoring result and work place.There were 172 men in high dose group and 116 men in low dose group.While 38 workers unexposed occupationally carcinogenic substances were selected as the control group,who were employed in medical therapy unit nearby 2 kilometers from steel factory.We investigated their general information,history of personal and occupational exposure,and the work environment.Blood samples were collected immediately after a shift at the end of a working day from 288 coke oven workers and 38 control workers.Levels of HSP90,HSP60 and HSP27 in peripheral blood lymphocytes were measured by Western blot.LDH and MDA were measured by ELISA. Chromosomal aberrations and the degree of DNA damage in peripheral blood lymphocytes were detected by comet assay.
Results There were no significant differences among those groups regarding age,sex, smoking and drinking habits(P＞0.05).Levels of HSP90(ratio)in peripheral blood lymphocytes in three groups were separately 0.24±0.32,0.12±0.30 and 0.06±0.33.They increased significantly compared with that of the control.But levels of HSP60 and HSP27 were not significantly different among those groups.Monitoring result of LDH appeared that the level of LDH in the high dose group((246.7±42.79)U/L)was higher than those in the low dose group ((205.7±33.72)U/L)and in the control group((199.7±31.78)U/L)(P＜0.05).Detectable result of MDA presented that the level of MDA in the high dose group((2.68±0.67)nmol/ml)was bigger than those in the low dose group((2.35±0.58)nmol/ml)and in the control group ((2.24±0.66)nmol/ml)(P＜0.05).Compared with the control group,there was significant difference in tail length,Olive Tail Moment of occupational exposure workers,high dose group＞low dose group＞control group(P＜0.05).The degree of DNA damage increased with the rising of exposure BaP dose(χ~2=36.411,P＜0.001;Spearman r=-0.345,P＜0.001).There is a dose-effect relationship between Olive and exposed dose of PAHs.(β=-0.117,P=0.030)
Conclusion 1.Result of comet assay showed that Coke oven emission could result in genetic damage.2.The increase of HSP90 level may be involved in protection of DNA from genotoxic damage induced by carcinogen.3.LDH and MDA in peripheral blood and HSP90 in peripheral blood of coke oven workers could offer scientific evidence for the study of an exposure biomarker to evaluate PAHs contact level.
引文
[1]WHO.International Programme on Chemical Safety.Environmental Health Criteria 202:selected non-heterocyclic polycyclic aromatic hydrocarbons.Geneva:World Health Organization,1998.883.
[2]Chen ML,Lee BC,Lu PL,et al.Polycyclic aromatic hydrocarbon-deoxyribonucleic acid(PAH-DNA)adduct levels and exposure to coke oven emissions among workers in Taiwan.Arch Environ Health,2003,58(5):298-305.
[3]Farmer PB,Singh R,Kaur B,et al.Molecular epidemiology studies of carcinogenic environmental pollutants.Effects of polycyclic aromatic hydrocarbons(PAHs)in environmental pollution on exogenous and oxidative DNA damage.Mutat Res,2003,544(2-3):397-402.
[4]Feng Z,Hu W,Rom WN,et al.Chromium(VI)exposure enhances polycyclic aromatic hydrocarbon-DNA binding at the p53 gene in human lung ceils.Carcinogenesis,2003,24(4):771-778.
[5]徐谦,杨进波,蒋长征.热休克蛋白70的表达在苯并[a]芘致DNA损伤中的作用.中华劳动卫生职业病杂志,2004,22(2):96-99.
[6]Rossner P Jr,Binkova B,Sram RJ.Heat shock proteins hsp32 and hsp70 as biomarkers of an early response? In vitro induction of heat shock proteins after exposure of cell culture to carcinogenic compounds and their real mixtures.Murat Res,2003,542(1-2):105-116.
[7]Lutz W,Nowakowska-Swirta E.Gene p53 mutations,protein p53,and anti-p53antibodies as biomarkers of cancer process.Int J Occup Med Environ Health,2002,15(3):209-218.
[8]张国高,贺涵贞,邬堂春.热应激蛋白及其在职业医学中应用研究的展望.中华劳动卫生职业病杂志,1998,16(2):67-69.
[9]邬堂春,贺涵贞,张国高.热应激蛋白研究的进展与前景.中华预防医学杂志,2000,34(1):6-7.
[10]段小丽,魏复盛.苯并[a]芘的环境污染健康危害及研究热点问题.世界科技研究与发展,2002,24(1):11-17.
[11]沈关心.外周血单核细胞的分离、纯化.见:沈关心,周汝麟,主编.现代免疫学实验技术.第2版.武汉:湖北科学技术出版社.1998,377-390.
[12]f.奥斯伯,等.《精编分子生物学实验指南》.科学技术出版社.1999.
[13]张建平.单细胞凝胶电泳技术及其应用.国外医学:遗传学分册.1997,20(5):231-234.
[14]冷曙光,牛勇,潘祖飞,等.彗星试验琼脂糖凝胶片保存方法研究[J].卫生研 究,2003,32(1):64.
[15]朱志良,庄志雄,黄钰,等.单细胞凝胶电泳图像分析系统的研制及应用[J].中华劳动卫生职业病杂志,2001,19(4):298-300.
[16]Andereson D,Yu TW,Philips BJ,et al.The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay.Mutat Res,1994,307:261-271.
[17]Popp W,Vahrenholz C,Schell C,et al.DNA single strand breakage,DNAadducts,and sister chromatid exchange in lymphocytes and phenanthreneand pyrene metabolites in urine of coke oven workers.Occup Environ Med.1997,54(3):176-183.
[18]Wei YQ,Zhao X,Kariya Y,et al.Inhibition of prolife ration and induction of apoptosis by abrogation of heat shock protein(HSP)70 expression in tumor cells.Cancer lmmunol lmmunother,1995,40(2):73.
[19]陈胜,海涛,王瑞波.焦炉工外周血淋巴细胞热应激蛋白70水平与DNA损伤的关系.中华劳动卫生职业病杂志,2000,18(6):324-326.
[20]姜苏蓉,刘莉,程蕴琳.热休克蛋白27抗细胞凋亡的分子机制.中华老年医学杂志,2004,23(2):138-140.
[21]海涛,陈胜,王瑞波,等.焦炉作业工人血浆热应激蛋白70kD抗体滴度及肿瘤坏死因子水平的研究.工业卫生与职业病,1998,24(6):343-345.
[22]Martin K J,Kritzman BM,Price LM,et al Linking gene expression patterns to therapeutic groups in breast cancer[J].Cancer Res,2000,60:2232-2238.
[23]Conroy SE,Latchman DS.Do heat shock proteins have a role in breast cancer?[J].Br J Lancer,1996,74:717-721.
[24]Kawanishi K,Shiozaki H,Doki Y.et al.Prognostic significance of heat shock proteins 27 and 70 in patients with squamous cell carcinoma of the esophagus[J].Cancer,1999,85:1649-1657.
[25]Jameel A,Skilton RA,Campbell TA,et al.Clinical and biological significance of HSP 89a in human breast cancer[J].Int J Cancer,1992,50:409-415.
[26]Ciocca DR,Fuqua SA,Lock-Lim S,et al Response of human In-east cancer cells to heat shock and chemotherapeutic drugs[J].Cancer Res,1992,52:3648-3654.
[27]徐耘,田华,徐勇,等.苯接触工人血浆热应激蛋白抗原和抗体水平探讨.中华预防医学杂志,2001,35(3):214.
[28]郑金平,孙健娅,郭亮.焦炉工人外周血淋巴细胞HSP72表达特征.中国公共卫生,2007,23(1):68-70.
[29]戴顺东,张秀伟,范垂峰,等.热休克蛋白90在抑制细胞凋亡中的作用.中国 医科大学学报,2006,35(3):233-234.
[30]陈奕,丁健.热休克蛋白90-癌症治疗的新靶点.癌症,2004,23(8):968-973.
[31]宋剑锋,邬堂春,毛福英.热应激蛋白在职业医学中的应用研究进展.湖北预防医学杂志,2000,11(1):13-14.
[32]Am J Med Sci9:339,1972.
[33]孙恩林,卢桥发,丁焱焱,等.焦炉作业工人血清SOD活性及脂质过氧化产物含量的研究.工业卫生与职业病,1998,24(16):346-348.
[34]桂晓美,杨德昌.乳酸脱氢酶同工酶的临床意义分析.检验医学,2005,20(1):3
[35]Ostling O,Johanson KJ.J Biochem Biophys Res Common,1984,123:291.
[36]Singh NP et al.Exp Cell Res,1988,175:184.
[37]Olive PL.Radiat Res,1989,117:79.
[38]Kassie F,Parzefall W,Knasmuller S.Single cell gel electrophoresis assay:an new technique for human biomonitoring studies.Mutat Res,2000,463:13-31.
[39]冷曙光,郑玉新,牛勇.焦炉作业工人多环芳烃暴露与外周血淋巴细胞DNA 损伤的关系.中华劳动卫生职业病杂志,2004,22(4):250-253.
[40]Xiao CF,Chen S,Li JZ,et al.Association of HSP70 and genotoxic damage in lymphocytes of workers exposed to coke oven emission[J].Cell Stress Chaperones.2002,7:396~402.
[41]高雅娟,陈胜,肖成峰.苯并(a)芘代谢产物作用下人胚肺细胞热应激蛋白70表达与DNA损伤.中华劳动卫生职业病杂志,2000,18(6):321-323.
[42]冷曙光,郑玉新,张文众,等.焦炉工外周血淋巴细胞遗传物质损伤水平的研究[J].中华劳动卫生职业病杂志,2004,22(1):29-32.
[43]Siwinska E,Mielzynska D,KapkaL.Association between urinary 1-hydroxypyrene and genotoxic effects in coke oven workers[J].Occup Environ Med,2004,61:10-17.
[44]陈波,胡云平,郑力行,等.炼焦职业暴露工人与对照人群尿中12羟基芘水平比较[J].中华预防医学杂志,2005,39(6):388-341.
[1]Welch WJ.Mammalian stress response:cell physiology,structure/function of stress proteins,and implication for medicine and disease.Physical Rev,1992,72:1063-1081.
[2]Nomura F,Aoki M,Forbess J,et al.Myocardial self-preservative effect of heat shock protein70 on an immature lamb heart[J].Ann-Thorac Surg,1999,68:1736.
[3]Yahav S,et al.Poult Sci,1997,76(10):1448-1434.
[4]Gabriel JE.et al.Br Poult Sci,1996,37(2):443-439.
[5]Rordorf G.et al.Neuron,1991,7(6):1043-1051.
[6]James DM.et al.JM ol cell cardiol,1995,27(2):873-882.
[7]Moriis SD.et al.J clin Invest,1996,97(3):706-712.
[8]张永亮,吴美筠,等.热休克蛋白的分类、基因调控及其功能.法医学杂志,1999,15(4):239-242.
[9]梁学松,马铁明.热休克蛋白及其研究概况.辽宁中医学院学报,2004,6(1).
[10]肖红,王泉云,廖刃,等.氯氨酮-咪唑安定对感染性休克大鼠血清肿瘤坏死因子心肌热休克蛋白70表达的影响[J].临床麻醉学杂志,2001,17(9):491.
[11]邬堂春,贺涵贞,张国高.热应激蛋白研究的进展与前景.中华预防医学杂志,2000,34(1):6-7.
[12]张章,苏东明,陈玺华.缺血预处理对缺血再灌注肝脏中HSP70表达的影响[J].山西医科大学学报,2001,32(5):393.
[13]王占明,鲁建国,赖大年,等.热休克蛋白70与肝脏缺血预处理延迟保护效应[J].第四军医大学学报,2001,22(13):1200.
[14]赵平,龙波,崔健君.孕鼠产前缺氧性适应后胎鼠、新生大鼠脑组织热休克蛋白70的表达[J].中华麻醉学杂志,2001,21(6):352.
[15]谭淼等.中华病理学杂志,1997,26(1):38-40.
[16]王泉云,肖红,廖刃,等.氯氨酮-咪唑安定对感染性大鼠心肌HSP70表达的影响[J].中华麻醉学杂志,200l,21(7):417.
[17]周立文,王焱林,万德宁.不同剂量氯氨酮对大鼠脑组织热休克蛋白70表达的影响.中华麻醉学杂志,1999,19:118.
[18]吴扬,邬堂春,陈胜,等.高温作业工作血清抗HSP70抗体水平的研究.职业卫生与病伤,1995,10(4),193-194.
[19]李琦,潘芳,岳文浩.热休克蛋白70在应激中的表达及对细胞免疫功能的影响.中国行为医学科学,2003,12(3):350-351.
[20]徐芸,田华,徐勇,等.苯接触工人血浆热休克蛋白抗原和抗体水平探讨.中华 预防医学杂志,2001,35(3):214.
[21]陈胜,黄美阶、朱海燕,等.苯接触工人血浆热反应蛋白70抗体滴度分析.中华预防医学杂志,2000,34(1):8.
[22]王长来,王自正,茅志成,等.高温中暑患者血浆中热应激蛋白(HSP70)及其抗体水平的意义.中华劳动卫生与职业病杂志,2000,18(1):36.
[23]梅韬,肖成峰,谢俊刚,等.铁路乘警血浆主要热应激蛋白抗体与高血压的关系.中华劳动卫生职业病杂志,2001,19(5):363.
[24]马金香,孙业恒,曹多志,等.HSP70与高血压关系初探.中华预防医学杂志,2000,(1):14.
[25]姜军松,杨志刚,马景虎,等.复发性阿弗他溃疡和HSP的关系.中华口腔医学杂志,2001,27(4):389.
[26]李正贤.HSP70相关蛋白在中耳乳突胆脂瘤中的表达与定位.中华耳鼻咽喉,2000,(1):58.
[27]李琳,陈惠祯,张广平.热休克蛋白27表达与卵巢癌预后.肿瘤,2001,21(4):288.
[28]肖成峰,陈胜,高亚娟,等.HSP7l在抗癌药物足草乙甙致成人肝细胞凋亡中的作用.中华劳动卫生职业病杂志,2000,18(2):78.
[29]郭爱林,隋延仿,曲萍,等.体外构建的HSP70-抗原肽诱导抗原肽特异性免疫反应[J].中国免疫学杂志,200l,17:584.
[2]Chen ML,Lee BC,Lu PL,et al.Polycyclic aromatic hydrocarbon-deoxyribonucleic acid(PAH-DNA)adduct levels and exposure to coke oven emissions among workers in Taiwan.Arch Environ Health,2003,58(5):298-305.
[3]Farmer PB,Singh R,Kaur B,et al.Molecular epidemiology studies of carcinogenic environmental pollutants.Effects of polycyclic aromatic hydrocarbons(PAHs)in environmental pollution on exogenous and oxidative DNA damage.Mutat Res,2003,544(2-3):397-402.
[4]Feng Z,Hu W,Rom WN,et al.Chromium(VI)exposure enhances polycyclic aromatic hydrocarbon-DNA binding at the p53 gene in human lung ceils.Carcinogenesis,2003,24(4):771-778.
[5]徐谦,杨进波,蒋长征.热休克蛋白70的表达在苯并[a]芘致DNA损伤中的作用.中华劳动卫生职业病杂志,2004,22(2):96-99.
[6]Rossner P Jr,Binkova B,Sram RJ.Heat shock proteins hsp32 and hsp70 as biomarkers of an early response? In vitro induction of heat shock proteins after exposure of cell culture to carcinogenic compounds and their real mixtures.Murat Res,2003,542(1-2):105-116.
[7]Lutz W,Nowakowska-Swirta E.Gene p53 mutations,protein p53,and anti-p53antibodies as biomarkers of cancer process.Int J Occup Med Environ Health,2002,15(3):209-218.
[8]张国高,贺涵贞,邬堂春.热应激蛋白及其在职业医学中应用研究的展望.中华劳动卫生职业病杂志,1998,16(2):67-69.
[9]邬堂春,贺涵贞,张国高.热应激蛋白研究的进展与前景.中华预防医学杂志,2000,34(1):6-7.
[10]段小丽,魏复盛.苯并[a]芘的环境污染健康危害及研究热点问题.世界科技研究与发展,2002,24(1):11-17.
[11]沈关心.外周血单核细胞的分离、纯化.见:沈关心,周汝麟,主编.现代免疫学实验技术.第2版.武汉:湖北科学技术出版社.1998,377-390.
[12]f.奥斯伯,等.《精编分子生物学实验指南》.科学技术出版社.1999.
[13]张建平.单细胞凝胶电泳技术及其应用.国外医学:遗传学分册.1997,20(5):231-234.
[14]冷曙光,牛勇,潘祖飞,等.彗星试验琼脂糖凝胶片保存方法研究[J].卫生研 究,2003,32(1):64.
[15]朱志良,庄志雄,黄钰,等.单细胞凝胶电泳图像分析系统的研制及应用[J].中华劳动卫生职业病杂志,2001,19(4):298-300.
[16]Andereson D,Yu TW,Philips BJ,et al.The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay.Mutat Res,1994,307:261-271.
[17]Popp W,Vahrenholz C,Schell C,et al.DNA single strand breakage,DNAadducts,and sister chromatid exchange in lymphocytes and phenanthreneand pyrene metabolites in urine of coke oven workers.Occup Environ Med.1997,54(3):176-183.
[18]Wei YQ,Zhao X,Kariya Y,et al.Inhibition of prolife ration and induction of apoptosis by abrogation of heat shock protein(HSP)70 expression in tumor cells.Cancer lmmunol lmmunother,1995,40(2):73.
[19]陈胜,海涛,王瑞波.焦炉工外周血淋巴细胞热应激蛋白70水平与DNA损伤的关系.中华劳动卫生职业病杂志,2000,18(6):324-326.
[20]姜苏蓉,刘莉,程蕴琳.热休克蛋白27抗细胞凋亡的分子机制.中华老年医学杂志,2004,23(2):138-140.
[21]海涛,陈胜,王瑞波,等.焦炉作业工人血浆热应激蛋白70kD抗体滴度及肿瘤坏死因子水平的研究.工业卫生与职业病,1998,24(6):343-345.
[22]Martin K J,Kritzman BM,Price LM,et al Linking gene expression patterns to therapeutic groups in breast cancer[J].Cancer Res,2000,60:2232-2238.
[23]Conroy SE,Latchman DS.Do heat shock proteins have a role in breast cancer?[J].Br J Lancer,1996,74:717-721.
[24]Kawanishi K,Shiozaki H,Doki Y.et al.Prognostic significance of heat shock proteins 27 and 70 in patients with squamous cell carcinoma of the esophagus[J].Cancer,1999,85:1649-1657.
[25]Jameel A,Skilton RA,Campbell TA,et al.Clinical and biological significance of HSP 89a in human breast cancer[J].Int J Cancer,1992,50:409-415.
[26]Ciocca DR,Fuqua SA,Lock-Lim S,et al Response of human In-east cancer cells to heat shock and chemotherapeutic drugs[J].Cancer Res,1992,52:3648-3654.
[27]徐耘,田华,徐勇,等.苯接触工人血浆热应激蛋白抗原和抗体水平探讨.中华预防医学杂志,2001,35(3):214.
[28]郑金平,孙健娅,郭亮.焦炉工人外周血淋巴细胞HSP72表达特征.中国公共卫生,2007,23(1):68-70.
[29]戴顺东,张秀伟,范垂峰,等.热休克蛋白90在抑制细胞凋亡中的作用.中国 医科大学学报,2006,35(3):233-234.
[30]陈奕,丁健.热休克蛋白90-癌症治疗的新靶点.癌症,2004,23(8):968-973.
[31]宋剑锋,邬堂春,毛福英.热应激蛋白在职业医学中的应用研究进展.湖北预防医学杂志,2000,11(1):13-14.
[32]Am J Med Sci9:339,1972.
[33]孙恩林,卢桥发,丁焱焱,等.焦炉作业工人血清SOD活性及脂质过氧化产物含量的研究.工业卫生与职业病,1998,24(16):346-348.
[34]桂晓美,杨德昌.乳酸脱氢酶同工酶的临床意义分析.检验医学,2005,20(1):3
[35]Ostling O,Johanson KJ.J Biochem Biophys Res Common,1984,123:291.
[36]Singh NP et al.Exp Cell Res,1988,175:184.
[37]Olive PL.Radiat Res,1989,117:79.
[38]Kassie F,Parzefall W,Knasmuller S.Single cell gel electrophoresis assay:an new technique for human biomonitoring studies.Mutat Res,2000,463:13-31.
[39]冷曙光,郑玉新,牛勇.焦炉作业工人多环芳烃暴露与外周血淋巴细胞DNA 损伤的关系.中华劳动卫生职业病杂志,2004,22(4):250-253.
[40]Xiao CF,Chen S,Li JZ,et al.Association of HSP70 and genotoxic damage in lymphocytes of workers exposed to coke oven emission[J].Cell Stress Chaperones.2002,7:396~402.
[41]高雅娟,陈胜,肖成峰.苯并(a)芘代谢产物作用下人胚肺细胞热应激蛋白70表达与DNA损伤.中华劳动卫生职业病杂志,2000,18(6):321-323.
[42]冷曙光,郑玉新,张文众,等.焦炉工外周血淋巴细胞遗传物质损伤水平的研究[J].中华劳动卫生职业病杂志,2004,22(1):29-32.
[43]Siwinska E,Mielzynska D,KapkaL.Association between urinary 1-hydroxypyrene and genotoxic effects in coke oven workers[J].Occup Environ Med,2004,61:10-17.
[44]陈波,胡云平,郑力行,等.炼焦职业暴露工人与对照人群尿中12羟基芘水平比较[J].中华预防医学杂志,2005,39(6):388-341.
[1]Welch WJ.Mammalian stress response:cell physiology,structure/function of stress proteins,and implication for medicine and disease.Physical Rev,1992,72:1063-1081.
[2]Nomura F,Aoki M,Forbess J,et al.Myocardial self-preservative effect of heat shock protein70 on an immature lamb heart[J].Ann-Thorac Surg,1999,68:1736.
[3]Yahav S,et al.Poult Sci,1997,76(10):1448-1434.
[4]Gabriel JE.et al.Br Poult Sci,1996,37(2):443-439.
[5]Rordorf G.et al.Neuron,1991,7(6):1043-1051.
[6]James DM.et al.JM ol cell cardiol,1995,27(2):873-882.
[7]Moriis SD.et al.J clin Invest,1996,97(3):706-712.
[8]张永亮,吴美筠,等.热休克蛋白的分类、基因调控及其功能.法医学杂志,1999,15(4):239-242.
[9]梁学松,马铁明.热休克蛋白及其研究概况.辽宁中医学院学报,2004,6(1).
[10]肖红,王泉云,廖刃,等.氯氨酮-咪唑安定对感染性休克大鼠血清肿瘤坏死因子心肌热休克蛋白70表达的影响[J].临床麻醉学杂志,2001,17(9):491.
[11]邬堂春,贺涵贞,张国高.热应激蛋白研究的进展与前景.中华预防医学杂志,2000,34(1):6-7.
[12]张章,苏东明,陈玺华.缺血预处理对缺血再灌注肝脏中HSP70表达的影响[J].山西医科大学学报,2001,32(5):393.
[13]王占明,鲁建国,赖大年,等.热休克蛋白70与肝脏缺血预处理延迟保护效应[J].第四军医大学学报,2001,22(13):1200.
[14]赵平,龙波,崔健君.孕鼠产前缺氧性适应后胎鼠、新生大鼠脑组织热休克蛋白70的表达[J].中华麻醉学杂志,2001,21(6):352.
[15]谭淼等.中华病理学杂志,1997,26(1):38-40.
[16]王泉云,肖红,廖刃,等.氯氨酮-咪唑安定对感染性大鼠心肌HSP70表达的影响[J].中华麻醉学杂志,200l,21(7):417.
[17]周立文,王焱林,万德宁.不同剂量氯氨酮对大鼠脑组织热休克蛋白70表达的影响.中华麻醉学杂志,1999,19:118.
[18]吴扬,邬堂春,陈胜,等.高温作业工作血清抗HSP70抗体水平的研究.职业卫生与病伤,1995,10(4),193-194.
[19]李琦,潘芳,岳文浩.热休克蛋白70在应激中的表达及对细胞免疫功能的影响.中国行为医学科学,2003,12(3):350-351.
[20]徐芸,田华,徐勇,等.苯接触工人血浆热休克蛋白抗原和抗体水平探讨.中华 预防医学杂志,2001,35(3):214.
[21]陈胜,黄美阶、朱海燕,等.苯接触工人血浆热反应蛋白70抗体滴度分析.中华预防医学杂志,2000,34(1):8.
[22]王长来,王自正,茅志成,等.高温中暑患者血浆中热应激蛋白(HSP70)及其抗体水平的意义.中华劳动卫生与职业病杂志,2000,18(1):36.
[23]梅韬,肖成峰,谢俊刚,等.铁路乘警血浆主要热应激蛋白抗体与高血压的关系.中华劳动卫生职业病杂志,2001,19(5):363.
[24]马金香,孙业恒,曹多志,等.HSP70与高血压关系初探.中华预防医学杂志,2000,(1):14.
[25]姜军松,杨志刚,马景虎,等.复发性阿弗他溃疡和HSP的关系.中华口腔医学杂志,2001,27(4):389.
[26]李正贤.HSP70相关蛋白在中耳乳突胆脂瘤中的表达与定位.中华耳鼻咽喉,2000,(1):58.
[27]李琳,陈惠祯,张广平.热休克蛋白27表达与卵巢癌预后.肿瘤,2001,21(4):288.
[28]肖成峰,陈胜,高亚娟,等.HSP7l在抗癌药物足草乙甙致成人肝细胞凋亡中的作用.中华劳动卫生职业病杂志,2000,18(2):78.
[29]郭爱林,隋延仿,曲萍,等.体外构建的HSP70-抗原肽诱导抗原肽特异性免疫反应[J].中国免疫学杂志,200l,17:584.