肿瘤致病因素.pptxVIP

会计学;一、化学因素与人类肿瘤关系的历史;The ames test for mutagenicity ;三、化学致癌物的分类;2、根据化学致癌物与 人类肿瘤的关系;3、环境因素分类;第6页/共57页;四、化学致癌机理;细胞色素P450依赖性酶（cytochrome P450-dependent enzymes，CYP） 作用机理：通过对致癌物的环氧化、羟化、脱烷基化、氧化还原结合以及水解，从而使致癌物活化或代谢成水解产物排出体外。 对化学致癌物的代谢具双重性。 细胞色素P450基因多态性与肿瘤关系的研究已逐步成为肿瘤流行病学研究的热点。;2、DNA加合物的形成 造成DNA损伤 影响DNA复制与转录 与特定的基因转变有关－癌基因和抑癌基因;五、化学致癌的特点;六、常见化学致癌物;第12页/共57页;（2）致癌机理： ;2、芳香胺类（aromatic amines）和偶氮染料（azodyes） 含苯环和氮原子的化学致癌物，主要是染料合成和药物化工原料 （1）、基本结构： 芳香胺 芳香酰胺;（2）、致癌机理：;3、亚硝基化合物（N-nitroso compounds, NOC） 具有R-N(NO)-R’结构的一类化合物 （1）、基本结构： 亚硝胺, 亚硝酰胺, 亚硝基氨基酸;（2）、致癌机理：;4、烷化剂类（alkylating agents） 一类具有烷化作用的有机分子 （1）、基本结构;第二节、致瘤病毒;致瘤病毒分类（RNADNA病毒）;与人类肿瘤相关的致瘤病毒;第22页/共57页;Human papillomavirus;1、 多瘤病毒;;乳头瘤状病毒与宫颈癌 How certain papillomaviruses are thought to give rise to cancer of the uterine cervix? E7与Rb结合 E6与p53结合;The viral E6 and E7 proteins inhibit and destabilize the tumor suppressors TP53 and RB1, respectively. Some cancers caused by HPV16 express E6 only, and show disruption of CDKN2A encoding p16INK4A. Others express E6 and E7 and in these p16INK4A is regularly overexpressed, since it is under feedback control by RB1 and further induced by continuous cell proliferation ;HPVs contain circular DNA genomes of 7.9 kb encoding 7 early and 2 late proteins with one control region (CR). While they replicate as circles, carcinogenicity requires integration of the viral genome into the cellular genome. Typically, the circle is opened within the E2 gene and several viral genes are lost. E6 and E7 expression is activated by cellular promoters or enhancers (this is pretty exactly the opposite of activation of cellular oncogenes by retroviral insertion): Because HPV infection is the initial step in the development of most cervical cancers, vaccination against HPV seems particularly promising for primary prevention of this cancer and is under development. ;5、乙型肝炎病毒与肝癌 X-蛋白与p53结合 myc基因重排 ras基因点突变;（1）DNA病毒感染宿主细胞后，根据宿主细胞的性质可分：;第31页/共57页;第32页/共57页;（2）、致瘤机理：;二、致瘤