职业性致癌因素PPT课件.ppt

职业性致癌因素与职业肿瘤 在工作环境中长期接触致癌因素 经过较长的潜伏期 而患某种特定的肿瘤 称职业性肿瘤 occupationaltumor 能引起职业性肿瘤的致癌因素 称职业性致癌因素 occupationalcarcinogen 1 1 职业性肿瘤的发病特点1 1好发部位多在致癌因素作用最强烈 最经常的部位发生或直接作用的靶器官 职业性癌的好发部位见下表 2 职业性癌的好发部位 摘自FischmanM L 等 1990 略有修改 职业接触发癌部位4 氨基联苯膀胱砷及砷化合物肺 皮肤 肝 血管肉瘤石棉胸膜与腹膜 间皮瘤 肺 喉 胃肠道 肾苯骨髓 白血病 联苯胺膀胱双氯甲醚肺六价化合物肺煤焦油沥青皮肤 阴囊 肺 膀胱煤焦油皮肤 阴囊 肺 膀胱电离辐射白血病 皮肤 其它 3 职业接触发癌部位未处理或轻度处理的矿物油肺芥子气肺 萘胺膀胱镍和镍化合物肺 鼻窦镭骨 肉瘤 氡肺页岩油皮肤 阴囊煤烟 焦油和油类皮肤 肺 膀胱含石棉纤维的滑石肺 间皮瘤紫外线皮肤氯乙烯肝 血管肉瘤 脑 肺 4 1 2发病条件第一所接触物质的化学结构第二接触途径第三接触剂量和时间1 3发病年龄平均42年 但有长有短 如苯致白血病 最短者仅需4个月 潜伏期多在10年以上 发病年龄以40 50最多见 较非职业性的早10 15年 5 致癌因素肿瘤部位潜伏期 年 沥青 煤焦油皮肤20 24矿物油皮肤50 54粗石蜡油皮肤15 18无机砷酸盐皮肤20 24肺25 48电离辐射皮肤20 30肺15 23骨髓 白血病 11 17骨骼 骨肉瘤 10 15石棉肺25 40胸腹膜20 40氯甲醚肺10 24切削油阴囊40 50芳香胺膀胱11 15 职业性肿瘤的潜伏期 6 1 4病理类型物不同而各具有一定的病理类型 例如铀矿工肺癌大部分为未分化小细胞癌 铬多致鳞癌 未分化小细胞癌 1 5高危职业有致癌危险的职业 据IARC资料 1987 略加整理 工业过程可能致癌因素铝生产多环芳烃金胺制造金胺靴 鞋制造及修理苯煤气制造 焦炭生产多环芳烃铸铁及铸钢多环芳烃 SiO2 金属烟异丙醇制造 强酸法 二异丙基硫酸酯 二丙基油品红制造品红 前身 即甲土立丁 镍冶炼氧化镍 低硫化镍橡胶工业芳香胺赤铁矿地下开采 氡 氡 7 2 职业性肿瘤的识别和确认 2 1临床观察阴囊癌与扫烟囱工作 家具制造与鼻窦癌 品红染料与膀胱癌等 2 2实验研究用可疑致癌物作动物诱变实验 观察能否诱发与人类相似的肿瘤 是证明职业因素致癌的重要依据之一 但动物与人有种属差异 8 2 3流行病调查 1 病因联系强度足够大 2 接触后果呈一致性 3 存在接触水平 反应关系 4 有其佐证资料 5 肿瘤发病的性别比例异常根据流行病学调查和动物实验研究结果 职业致癌物可分为三类 确认致癌物 可疑致癌物 潜在致癌物 9 确认的主要职业性致癌物 致癌物致癌部位致癌物致癌部位煤焦油唇 皮肤 鼻砷皮肤 肺 喉等苯并 a 芘肺 皮肤 萘胺 萘胺膀胱 肾盂等沥青皮肤联苯胺 4 氨基泌尿系统页岩油皮肤芥子气肺 气管 喉 鼻矿物油皮肤 喉氯甲醚 双氯甲醚肺石蜡皮肤异丙基油鼻窦 喉 肺碳黑皮肤氯乙烯肝木馏油皮肤 唇氯丁二烯皮肤 肺石棉肺 胸膜苯白血病铬酸盐鼻腔 喉 肺硬木尘鼻镍及其盐类鼻腔 鼻窦 肺 喉放射性物质肺 皮肤 白血病 骨瘤 10 某些疑似职业性致癌物 但缺乏证据 据1987IARC资料 略有修改 职业接触发癌部位动物人乙醛鼻粘膜1 3 丁二烯淋巴瘤 肺 胃 肝四氯化碳肝三氯甲烷肝 肾氯酚及苯氧基乙酸软组织肉瘤及淋巴瘤除草剂DDT肝 肺 淋巴瘤1 2 二溴 3 氯丙烷鼻腔 肺 胃对 二氯苯肝 肾二氯甲烷肺 肝 11 职业接触发癌部位动物人1 4 二恶烷肝 鼻腔表氯醇鼻腔 前胃呼吸道二溴化乙烯前胃 皮肤 肺乙烯硫脲甲状腺六六六 六氯化笨 肝白血病肼肺 肝 乳腺 鼻腔铅化合物 无机 肾4 4 甲撑双氯苯胺肺 肝 乳腺膀胱多溴化联苯肝TCDD肝 肺 其他软组织肉瘤 淋巴瘤四氯乙烯肝 白血病 12 3 化学致癌机制3 1化学致癌机制 1 体细胞突变学说 2 非遗传机制学说 3 癌基因学说 癌基因和抗癌基因 癌基因如 ras基因 ras与myc基因 抗癌基因如p53 HSPs 4 近来肿瘤与细胞凋亡 apoptosis 的研究颇受重视 细胞凋亡或称程序性细胞死亡 programmedcelldeath 热应激蛋白 heatstressproteins HSPs 13 3 2致癌机制研究的实际应用 1 检测致癌物和促癌物短期实验的建立 2 促进抗癌的研究 3 癌基因蛋白用于癌症早期诊断 14 4 我国八种法定职业性肿瘤4 1石棉所致肺癌 间皮瘤4 2联苯胺所致膀胱癌4 3苯所致白血病4 4氯甲醚所致肺癌4 5砷所致肺癌及皮肤癌4 6氯乙烯所致肝血管肉瘤4 7焦炉工人肺癌4 8铬酸盐制造工人肺癌 15 5 职业性肿瘤的预防原则5 1加强对职业性致癌因素的控制和管理5 2对致癌剂的限制与使用定出规程5 3加强宣传教育讲究个人卫生5 4逐渐建立致癌危险性预测制度 16 cancer Neoplasmsarediseasescharacterizedbyabnormalproliferationofcells Iftheproliferatingcellsdonotinvadesurroundingtissues theresultoftumorisbenign iftheydo itismalignant Somebenignneoplasmsmaybefatal includinghistologicallybenignbraintumorsthatgrowanddisplacenormalbraintissueintheconfinedspaceoftheskull andhepatocellularadenomasthatruptureandcausebleedingintotheperitonealcavity 17 DESCRIPTIVEEPIDEMIOLOGY ClassificationCancersareclassifiedaccordingtotheirorganortissueoforigin siteortopographycode andhistologicalfeatures morphologycode ICD 9SourcesofincidenceandMortalityRatesMagnitudeoftheCancerProblemRelativeImportanceofSpecificNeoplasms 18 Age adjustedincidence mortality and5 yearsurvivalratesinmenandwomenintheUnitedStates Rates per100 000 IncidenceMortality5 yearRelativeSurvival SitemalefemalemalefemalemalefemaleBuccalcavityandpharynx16 26 24 61 748 460 2Digestivesystem96 761 852 331 342 045 0Respiratorysystem92 244 077 632 217 517 7Bonesandjoints1 00 80 50 357 968 2Skin21 210 94 41 953 189 9Breast0 9109 60 227 183 983 2Femalegenitalsystem 48 0 14 9 67 6Malegenitalsystem146 9 26 5 86 3 Urinarysystem43 114 110 84 175 766 0Brainandnervoussystem7 55 25 13 528 129 9Endocrinesystem3 37 10 70 685 693 4Lymphomas21 514 38 65 552 960 7Leukemias13 47 88 44 941 038 7Allsites485 0345 0219 6141 552 360 1 19 AgeSexANNUALINCIDENCEOFSELECTEDCANCERSINCHILDRENUNDERAGE151980TO1992Ages0 14SiteMaleFemaleAllsites15 012 9Boneandjoint0 60 8Brainandothernervous3 63 0Hodgkin sdisease0 70 5Kidneyandrenalpelvis0 80 8Leukemias4 63 8Acutelymphocytic3 72 9Non Hodgkin slymphomas1 20 4Softtissue0 80 8 20 CriteriaforCausalityGeneralEtiologicalConsiderationTobaccoAlcoholIndustrialExposuresEnvironmentalPollutionNonionizingRadiationIonizingRadiationExogenousSexHormonesInfectiousAgentsNutritionandPhysicalActivityReproductiveFactorsGeneticFactors ETIOLOGYANDPRIMARYPREVENTION 21 ReductioninMortalityifFactorGoalGoalMet SmokingReduceprevalenceto1516 by1990by20008DietReducefatto30 ofcaloriesand8increasefiberto20to30g dayScreeningMammogramsin80 of50 70yearoldsPapsmearsin90 of20 39yearolds 80 of40 70yearolds3treatmentincreaseuseofstate of the arttherapy10 26 NATIONALCANCERINSTITUTE SGOALSFORIMPROVEDCANCERMORTALITYBYTHEYEAR2000 22 Smoking1994DeathsCancerRelativeAttributableDuetoSiteRiskRisk SmokingLung10 085 1130 163Larynx8 080 93 074Oralcavity4 079 06 259Esophagus3 075 47 845Bladder2 040 14 252Pancreas2 028 57 386Stomach1 835 75 000Kidney1 532 93 722 ASSOCIATIONOFCIGARETTESMOKINGWITHCANCERSATSELECTEDSITES 23 SpecificExposuresSiteorTumorType4 AminobiphenylBladderArsenicandarseniccompoundsLung skinAsbestosLung mesotheliomaBenzeneLeukemiaBenzidineBladderBerylliumandberylliumcompoundsLungCadmiumandcadmiumcompoundsLungChromiumcompoundsLung sinonasalCoaltarpitchesSkin lung bladderCoaltarsSkinErioniteMesotheliomaEthyleneoxideLeukemia lymphomaMineraloils untreatedandSkinmildlytreated2 NaphthylamineBladderNickelandnickelcompoundsSinonasal lung OCCUPATIONALCAUSESOFCANCER 24 IndustrialprocessSiteorTumorTypeAluminumproductionLung bladder lympho sarcomasandreticulosarcomasManufactureofauramineBladderBootandshoemanufactureNose bladderandrepairCoalgasificationLung bladder skinCokeproductionLung bladder skinFurnitureandcabinetmakingNoseHematitemining underground withexposuretoradonLungOccupationalexposuretostrong inorganic acidLung larynx nasalsinusIronandsteelfoundingLungManufactureofmagentaBladderPaintersLung larynx esophagus stomach bladder leukemia lymphomaRubberindustryBladder leukemia lymphoma OCCUPATIONALCAUSESOFCANCER 25 PERECENTAGEOFU S CANCERCASESANDDEATHSMOSTPROBABLYATTRIBUTABLETOVARIOUSACCEPTEDCAUSESOFCANCER NewCasesTotalCancerCauseMaleFemaleDeathsTobacco302030Alcoholandtobacco423Occupation524Drugs 1 1 1Ionizingradiation111Sunlight10102Infectiousagents355Totalpercentage 54 4146 26 SCREENINGANDSECONDARYPREVENTION PlanningaScreeningProgram1 Thesensitivityandspecificityoftestsorproceduresusedforscreening2 Thetargetspopulation3 Theprevalenceofthediseaseinthetargetpopulation4 Thepredictivevalueofapositivetest5 Theconsequencesoffalse positivetests6 Consequencesofafalse negativetest7 Applicabilityofthetest8 Acceptabilityofthetest9 Adverseconsequencesofthetest10 theevaluabilityoftheprogram 27 WorksofMylabrelatedtothisfield 28 InducingFactorsofHeatshockproteins Environmentalstresses heat ultravioletradiation heavymetals andcarbonmonoxide BaPetalVerycommoninlivingandworkingenvironmentsPathologicalstimuli viral bacterialandparasiticinfections fever inflammation malignancyandautoimmunityPhysiologicalstimuli cellgrowth celldifferentiation hormonalstimulationortissuedevelopment 29 TheImportantBiologicalFunctionsofHsps ThermotoleranceandTolerancetomanyharmfulchemicalsChaperonesTheprotectionofDNAGrowthandDevelopment 30 Stresses Diseases Hsps anti Hsps Mechanisms Biomarkers Others 31 Signaltransductionofstressresponse Stresses HSFgene heatshockfactor HSF HSF proteins HSE heatshockelement HSE HSPs proteins HSPsmRNA HSPs 32 BaP影响HSP70基因表达可能的模式图 HSP70mRNAHSP70 ERK1 2JNK1 2P38 NOS HSF1 维生素 凋亡 33 InvitrostudyontheroleofHsp70expressioninDNAdamageinhumanembryoniclungcellsexposedtobenzo a pyrene GaoY ChenS XiaoC WangR HeH TanguayRM WuT BiomedEnvironSci 2003 inPress 34 Bezeneapyrene BaP B a P Benzo a Pyrene isthoughttobeprocarcinogensandtoxicantswhichcommonlyandwidelyexistinlivingandworkingenvironmentsEpidemiologicaldatahavealsoshownanassociationbetweenB a PexposureandanincreasedincidenceofcertaincancersinhumansB a Panditsreactivemetabolitesareconsideredtobeprototypecompoundsthatexhibitmanyofthecytotoxic mutagenicandcarcinogeniceffectscharacteristicofPAHs 35 EffectsofB a PonDNAtaillength totallengthratioinHELcells n 25 36 37 38 39 40 41 42 Environmentalworkingconditionsinsixgroupsofworkers Valuesaremean S D P 0 05 comparedwithgroup6 control 43 IncidenceofantibodiesagainstHsp70inplasmaofworkers P 0 05 P 0 01comparedwithgroup6 44 Univariatelogisticregressionanalysisofriskfactorsinhypertension OR Oddsratio 45 Multivariatelogisticregressionanalysisoftheriskfactorsofhypertension 160 95mmHg OR oddsratio 46 MultivariatelogisticregressionanalysisoftheassociationofantibodiestoHsp70withhypertension OR Oddsratio 47 MultivariatelogisticregressionanalysisoftheassociationofantibodiestoHsp70withharshworkingconditions OR oddsratio 48 Conclusion HarshworkplaceconditionscanincreasetheproductionofantibodiesagainstHsp70 Thepresenceofantibodiestothisstressproteinmaybeassociatedwithhypertension 49 50 AssociationofH