DNA损伤及修复_第1页
DNA损伤及修复_第2页
DNA损伤及修复_第3页
DNA损伤及修复_第4页
DNA损伤及修复_第5页
已阅读5页,还剩5页未读 继续免费阅读

下载本文档

版权说明:本文档由用户提供并上传,收益归属内容提供方,若内容存在侵权,请进行举报或认领

文档简介

1、DNA repair pathways as targets for cancer therapyu DNA-damage agents in cancer treatmentu Efficient repair of chemotherapy lesionsu DNA repair inhibitors in combination therapyContentsDNA-damage agents 1. Radiotherapy and radiomimetics u Ionizing radiation can cause single-strand breaks (SSBs) and d

2、ouble-strand breaks (DSBs) in the DNA double helix backbone. u Radiomimetic agents Bleomycin(博来霉素) cause replication-independent DSBs that can kill non-replicating cells,such treatments can also rapidly prevent DNA replication by activation of cell-cycle checkpoints to avoid formation of toxic DNA r

3、eplication lesions.DNA-damage agents 2. Alkylating agents u Monofunctional alkylating agents(单功能烷化剂)(单功能烷化剂) Have one active moiety that modifies single bases. Alkylsulphonates(烷基磺酸盐), Nitrosourea compounds(亚硝基脲化合物), Temozolomide(替莫唑胺)u Bifunctional alkylating agents (双功能烷化剂)(双功能烷化剂) Have two reacti

4、ve sites and crosslink DNA with proteins or, alternatively, crosslink two DNA bases within the same DNA strand or on opposite DNA strands. Nitrogen mustard(氮芥),Mitomycin C (丝裂霉素C),Cisplatin(顺铂)等 DNA-damage agents3. Antimetabolites u Methotrexate(甲氨蝶呤),5-fluorouracil (5-FU) and 6-Mercaptopurine (6-巯基

5、嘌呤), resemble nucleotides, nucleotide precursors or cofactors required for nucleotide biosynthesis and act by inhibiting nucleotide metabolism pathways, thus depleting cells of dNTPs.u They can also impair replication fork(复制叉) progression by becoming incorporated into the DNA.DNA-damage agents4. To

6、poisomerase inhibitors u Topoisomerases are a group of enzymes that resolve torsional strains imposed on the double helix during DNA replication, they induce transient DNA breaks to relax supercoiled DNA or allow DNA strands to pass through each other.u Inhibitors:Camptothecins(喜树碱), Etoposide (VP16

7、,依托泊苷)5. Replication inhibitors u Aphidicolin(阿非科林,抗感染/抗病毒), Hydroxyurea(羟基脲)A panoply of DNA repair mechanisms maintains genomic stability.单链断裂 双链断裂错配/插入/缺失烷基化BER, base excision repair(碱基切除修复); NER, nucleotide excision repair(核酸切除修复);Homologous recombination:同源重组NHEJ, non-homologous end joining(非同源末端连接);大量加合物Efficient repair of chemotherapy les

温馨提示

  • 1. 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。图纸软件为CAD,CAXA,PROE,UG,SolidWorks等.压缩文件请下载最新的WinRAR软件解压。
  • 2. 本站的文档不包含任何第三方提供的附件图纸等,如果需要附件,请联系上传者。文件的所有权益归上传用户所有。
  • 3. 本站RAR压缩包中若带图纸,网页内容里面会有图纸预览,若没有图纸预览就没有图纸。
  • 4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
  • 5. 人人文库网仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对用户上传分享的文档内容本身不做任何修改或编辑,并不能对任何下载内容负责。
  • 6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
  • 7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。

评论

0/150

提交评论