DNA瞬态损伤的快速修复阻断癌变最早事件的发展  

The Earliest Stage of Carcinogenesis Blocked by the Fast Repair of DNA Transient Damage

作　　者：郑荣梁[1] 王春明[1] 林昌俊[1] 石益民[1] 李忌[1] 赵晨阳[1] 张琪[1] 黄双盛[1] 牟萍[1] 谭晓荣[1] 

机构地区：[1]兰州大学生命科学学院生物物理研究所,兰州730000

出　　处：《生物物理学报》2012年第3期185-199,共15页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(29972017;39870902;39270193);教育部中法合作研究项目(001230);科技部中法先进研究计划(SI00-05)~~

摘　　要：DNA瞬态损伤(DNA自由基)引起DNA碱基对断裂和双螺旋结构下沉,导致基因失稳,可能是构成癌变的最早事件。基因失稳是癌的共同特征标志之一,而DNA修复可通过维持基因完整性来降低癌的发生。修复DNA的能力低下也是癌的共同特征标志之一。近年新发现了一种独特的修复机制,称为快速修复,专一地修复DNA瞬态损伤,只需几个微秒就能完成,比已知的酶性修复快十亿倍,修复速率常数达到109L.mol-1.s-1。还发现凡是具有快速修复能力的植物多酚类几乎都能不同程度地削弱癌的特征标志,包括使癌细胞形态正常化、抑制癌细胞增殖、促进癌细胞分化或凋亡、降低端粒酶活性、减少植瘤率、阻止细胞迁移和扩散、抑制血管生成、延长存活时间、降低患癌风险等。DNA transient damage, DNA radicals, induces DNA base pair bond broken and double helix sunken, finaly destabilizes genomic integrity, which is one hallmark of most cancers. DNA repair maintains the genomic integdty reducing the onset of cancer. Various types of cancer involve defect in DNA repair. A novel and distinct repair mechanism, fast repair, has been recognized only in the recent years, is initiated and finished in a microsecond time scale, enormously faster by approximately 9 orders than enzymatic repair. The fast repair reaction rate constants are within 10^9 L .mol^-1 .s^-1 Thus fast repair mechanism eradicates the headstream of DNA damage, DNA radicals, on the earliest stage of carcinogenesis, and therefore maintains genome integrity, finally prevents incipient cancers from developing and cure preexisting cancers. Almost all the tested phytopolyphenols with fast repairing activity, except one, are able to suppress hallmarks of cancer, such as morphological normalization, redifferentiation, decrease of cancer growth and transplanting rate, inhibition of telomerase, metastasis, angiogenesis, in vitro and in vivo, reducing cancer incidence and mortality rate in animals.

关 键 词：DNA损伤 DNA快速修复 癌的特征标志 植物多酚类 

分 类 号：Q279[生物学—细胞生物学]