Balancing repair and tolerance of DNA damage caused by alkylating agents

被引：774

作者：

Fu, Dragony

Calvo, Jennifer A.

Samson, Leona D. ^{[1
]}

机构：

[1] MIT, Ctr Environm Hlth Sci, David H Koch Inst Integrat Canc Res, Dept Biol Engn, Cambridge, MA 02139 USA

来源：

NATURE REVIEWS CANCER | 2012年 / 12卷 / 02期

基金：

美国国家卫生研究院;

关键词：

BASE EXCISION-REPAIR; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE MGMT; APURINIC/APYRIMIDINIC ENDONUCLEASE APE1; RETROVIRUS-MEDIATED EXPRESSION; SMALL-MOLECULE INHIBITORS; METHYL-N-NITROSOUREA; HAMSTER OVARY CELLS; IN-VIVO SELECTION; PHASE-II TRIAL; MISMATCH REPAIR;

D O I：

10.1038/nrc3185

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

引用

页码：104 / 120

页数：17

共 210 条

[1]

Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers [J].