細(xì)胞癌變及誘導(dǎo)因素主講老師：徐單單CellularcarcinogenesisandinducingfactorsGuangdongFoodandDrugVocationalCollege廣東食品藥品職業(yè)學(xué)院腫瘤概述01TumorOverview細(xì)胞惡性轉(zhuǎn)化及誘導(dǎo)因素02Malignanttransformationofcellsandinducingfactors01腫瘤概述TumorOverview腫瘤概述TumorOverview癌癥已成為人類(lèi)健康的第一大殺手，每年全世界新出現(xiàn)的癌癥病例為500-700萬(wàn)，中國(guó)為180-200萬(wàn)。Cancerhasbecomethenumberonekillerofhumanhealth,with5-7millionnewcancercasesworldwideeachyear,and1.8-2millioninChina腫瘤：是機(jī)體遺傳和環(huán)境因素以協(xié)同或序貫的方式，引起遺傳物質(zhì)DNA損傷、突變，同時(shí)伴隨有多個(gè)癌基因激活和腫瘤抑制基因失活，使正常細(xì)胞不斷增生、轉(zhuǎn)化形成新的生成物，常表現(xiàn)為局部腫塊。Tumor:Itiscausedbythesynergisticorsequentialcombinationofgeneticandenvironmentalfactorsinthebody,resultinginDNAdamageandmutationofgeneticmaterial,accompaniedbyactivationofmultipleoncogenesandinactivationoftumorsuppressorgenes,causingnormalcellstocontinuouslyproliferateandtransformintonewproducts,oftenmanifestedaslocaltumors.腫瘤細(xì)胞具有異常的形態(tài)、代謝和功能。Tumorcellshaveabnormalmorphology,metabolism,andfunction.它生長(zhǎng)旺盛，常持續(xù)生長(zhǎng)。Itgrowsvigorouslyandoftencontinuestogrow腫瘤的發(fā)生是一個(gè)長(zhǎng)期的、多階段、多基因改變累計(jì)的過(guò)程，具有多基因控制和多因素調(diào)節(jié)的復(fù)雜性。Theoccurrenceoftumorsisalong-term,multi-stage,andmultigeneaccumulationprocess,withthecomplexityofmultigenecontrolandmultifactorregulation.良性腫瘤Benigntumors惡性腫瘤Malignanttumors02細(xì)胞惡性轉(zhuǎn)化及誘導(dǎo)因素Malignanttransformationofcellsandinducingfactors細(xì)胞惡性轉(zhuǎn)化及誘導(dǎo)因素Malignanttransformationofcellsandinducingfactors

腫瘤是一種細(xì)胞病，腫瘤發(fā)生的本質(zhì)是細(xì)胞的遺傳物質(zhì)——基因組DNA，所攜帶的遺傳信息發(fā)生病理改變而造成的細(xì)胞病，亦即由于多基因內(nèi)的結(jié)構(gòu)或功能改變的積累而導(dǎo)致細(xì)胞的增值失控和分化異常，以致細(xì)胞突變獲得兩種基本特性：Tumorisacellulardisease,andtheessenceoftumoroccurrenceisthepathologicalchangesinthegeneticinformationcarriedbythegeneticmaterialofcells-genomicDNA.Thisiscausedbytheaccumulationofstructuralorfunctionalchangesinmultiplegenes,leadingtouncontrolledproliferationandabnormaldifferentiationofcells,resultinginmutantcellsacquiringtwobasiccharacteristics：腫瘤是什么樣的疾??？Whatkindofdiseaseisatumor?以上兩個(gè)特征相結(jié)合造成腫瘤細(xì)胞的轉(zhuǎn)移、播散。腫瘤細(xì)胞可將上述特征傳給子代細(xì)胞，在細(xì)胞水平進(jìn)行遺傳。Thecombinationoftheabovetwocharacteristicscausesthemetastasisanddisseminationoftumorcells.Tumorcellscanpassontheabovecharacteristicstooffspringcellsforinheritanceatthecellularlevel不衰老、不凋亡、不斷增殖，即不該增長(zhǎng)仍不停增長(zhǎng)，該死而不死Noaging,noapoptosis,andcontinuousproliferation,thatis,itshouldnotgrowbutstillcontinuestogrow,dyingbutnotdying侵襲到不該侵襲的部位Invasiontoareasthatshouldnotbeinvaded

外界因素Externalfactors化學(xué)因素

Chemicalfactors烷化劑：有機(jī)農(nóng)藥、硫芥等，可致肺癌及造血器官腫瘤。Alkylatingagents:organicpesticides,sulfurmustard,etc.,cancauselungcancerandhematopoieticorgantumors芳香烴化合物、亞硝酸與亞硝酸鹽。

Aromaticcompounds,nitrousacid,andnitrite

有些化學(xué)致癌物可直接致癌，引起點(diǎn)突變，例如Somechemicalcarcinogenscandirectlycausecancerandtriggerpointmutations,suchasDNA加合劑：如苯并芘，在體內(nèi)代謝后生成四羥苯并芘，與嘌呤共價(jià)結(jié)合引起損傷。DNAadductors,suchasbenzo[a]pyrene,aremetabolizedinthebodytoproducetetrahydroxybenzo[a]pyrene,whichcovalentlybindstopurinesandcausesdamage.堿基類(lèi)似物：如5-FU，6-MP等，可摻入到DNA分子中引起損傷或突變。

Baseanalogues,suchas5-FU,6-MP,etc.,canbeincorporatedintoDNAmoleculestocausedamageormutation斷鏈劑：如過(guò)氧化物，含巰基化合物等，可引起DNA鏈的斷裂。Chainscissionagents:suchasperoxides,thiolcontainingcompounds,etc.,cancauseDNAstrandbreakage由紫外線、電離輻射、X射線等引起的DNA損傷。DNAdamagecausedbyultravioletradiation,ionizingradiation,X-rays,etc.其中，X射線和電離輻射常常引起DNA鏈的斷裂，而紫外線常常引起嘧啶二聚體的形成，如TT，TC，CC等二聚體。Amongthem,X-raysandionizingradiationoftencauseDNAstrandbreaks,whileultravioletradiationoftenleadstotheformationofpyrimidinedimerssuchasTT,TC,CC,andotherdimers.物理因素

Physicalfactors這些嘧啶二聚體由于形成了共價(jià)鍵連接的環(huán)丁烷結(jié)構(gòu)，

因而會(huì)引起復(fù)制障礙。Thesepyrimidinedimerscancausereplicationbarriersduetotheformationofcovalentlylinkedcyclobutanestructures生物因素

Biologicalfactors

一些腫瘤與病毒、細(xì)菌及寄生物的感染有關(guān)，已知的致癌病毒有：

Sometumorsareassociatedwithinfectionsbyviruses,bacteria,andparasites.Knowncarcinogenicvirusesinclude:生物因素

BiologicalfactorsDNA病毒：HBV（肝癌）、HPV（宮頸癌、食管癌）、EBV（鼻咽癌）。DNAviruses:

HBV(livercancer),HPV(cervicalcancer,esophagealcancer),

EBV(nasopharyngealcancer)RNA病毒：HCV（肝癌）、HIV（卡波氏肉瘤）RNAviruses:

HCV(livercancer),HIV(Kaposi'ssarcoma)此外，寄生蟲(chóng)與腫瘤有關(guān)，如埃及血吸蟲(chóng)可致膀胱癌，日本血吸蟲(chóng)對(duì)大腸癌有促進(jìn)作用。Inaddition,parasitesarerelatedtotumors.Forexample,Schistosomaaegypticancausebladdercancer,andSchistosomajaponicumcanpromotecolorectalcancerLossofgeneticmaterial,activationofoncogenesorinactivationoftumorsuppressorgenes遺傳物質(zhì)丟失，癌基因活化或抑癌基因失活；Hormonesrelatedtotumorigenesis,specificallyestrogenandprolactinarerelatedtobreastcancer與腫瘤發(fā)生有關(guān)的激素，較為明確的是雌激素和催乳素與乳腺癌有關(guān)；

內(nèi)在因素Internalfactors遺傳因素

Geneticfactors內(nèi)分泌因素

EndocrinefactorsIndividualswithinnateoracquiredimmunedeficienciesarepronetodevelopingmalignanttumors,suchasthosewithacquiredautoimmunediseases先天或后天免疫缺陷者易發(fā)生惡性腫瘤，如獲得性自身免疫性疾病易發(fā)生惡性腫瘤。免疫因素

ImmunefactorsDiseaseswithimmunoglobulindeficiencyarepronetoleukemiaandlymphaticsystemtumors丙種球蛋白缺乏癥疾病易患白血病和淋巴系統(tǒng)腫瘤。免疫抑制劑長(zhǎng)期服用，腫瘤發(fā)生率較高。Longtermuseofimmunosuppressantsincreasestheincidenceoftumors.圖1.各種致癌因素引起的腫瘤發(fā)生率Figure1.Tumorincidencecausedbyvariouscarcinogenicfactors35%32%數(shù)據(jù)來(lái)源于