Oxidative DNA damage background estimated by a system model of base excision repair.
Oxidative DNA damage background estimated by a system model of base excision repair.
复制标题
通过碱基切除修复系统模型估计氧化 DNA 损伤背景。
DOI：
10.1016/j.freeradbiomed.2004.05.003
复制
发表时间：
2004
影响因子：
7.4
通讯作者：
Wilson3rd,DavidM
中科院分区：
文献类型：
--
作者：
Sokhansanj,BahradA;Wilson3rd,DavidM
Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level, based on measuring 8-oxoguanine lesions as a biomarker, have led to estimates that vary over three to four orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our findings show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.
