肿瘤致病因素.pptVIP

第二节、致瘤病毒?1908，Ellermann及Bang无细胞滤液证实病毒与恶性肿瘤有病因学上的关系。?1911，Rous用滤液成功诱发鸡的白血病和肉瘤。?1933，Shope将病毒所致的野兔乳头状瘤进行皮下移植试验,发生浸润性鳞癌。?1934，Lucke观察到冻干的无细胞提取物可传播蛙肾癌。?1936，Bittner含致瘤病毒的乳汁可将鼠的乳腺癌传给子代。?50年代发现鼠白血病是由病毒引起的。?60年代在显微镜下证实了这种病毒的形态。?1962，Burkitt发现病毒可引起淋巴瘤。?1964，Epstein和Barr在Burkitt淋巴瘤的细胞培养液中发现该病毒，命名为EB病毒。致瘤病毒分类（RNADNA病毒）与人类肿瘤相关的致瘤病毒一、致瘤性DNA病毒DNA肿瘤病毒的分类多瘤病毒科乳头状瘤病毒科腺病毒科疱疹病毒科乙型肝炎样病毒Humanpapillomavirus?SV40病毒两种肿瘤抗原(Tummorant’T抗原)其分子是分别为94kd(大T抗原)和17kd(小t抗原)。01?T抗原与诱发癌主细胞有关，T抗原为细胞转化的启动所必须,具有转化细胞功能，转化细胞表型的维持必需有大T抗原的持续性表达。02?t抗原对于细胞的转化不是必需的，但可起加强作用。03?大T抗原大部分存在于转化细胞的核内，与Rbp53相互作用。041、多瘤病毒Somestrainscausebenignlesionsoftheepidermisandotherepithelia,whileotherscausemalignancies,particularofthecervix,thepenis,theanogenitalregion,andlikelyalsooftheepidermisandsquamousepitheliaoftheheadandneck.ThedifferencesbetweenthestrainscanbetracedtodifferencesinthepotencyoftheirencodedE6andE7proteins.ThemostprevalentoncogenicstrainisHPV16.ManywomenandmenareinfectedbyHPV,butonlysomedevelopcancers.Thisispartlyduetostraindifferences,andpartlytodifferencesintheabilityofanindividual’simmunesystemtoclearthevirusandrepairthelesionsintheinfectedtissues.2、乳头状病毒科Humanpapillomaviruses乳头瘤状病毒与宫颈癌Howcertainpapillomavirusesarethoughttogiverisetocanceroftheuterinecervix?E7与Rb结合E6与p53结合TheviralE6andE7proteinsinhibitanddestabilizethetumorsuppressorsTP53andRB1,respectively.SomecancerscausedbyHPV16expressE6only,andshowdisruptionofCDKN2Aencodingp16INK4A.OthersexpressE6andE7andinthesep16INK4Aisregularlyoverexpressed,sinceitisunderfeedbackcontrolbyRB1andfurtherinducedbycontinuouscellproliferationHPVscontaincircularDNAgenomesof7.9kbencoding7earlyand2lateproteinswithonecontrolregion(CR).Whiletheyreplicateascircles,carcinogenicityrequiresintegrationoftheviralgeno