Oxidative DNA damage background estimated by a system model of base excision repair

Sokhansanj, B A

doi:10.1016/j.freeradbiomed.2004.05.003

Title: Oxidative DNA damage background estimated by a system model of base excision repair

Journal Article · Thu May 13 00:00:00 EDT 2004 · Free Radical Biology and Medicine

DOI:https://doi.org/10.1016/j.freeradbiomed.2004.05.003· OSTI ID:15014200

Sokhansanj, B A

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 varying over 3-4 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 results 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.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: W-7405-ENG-48

OSTI ID:: 15014200

Report Number(s):: UCRL-JRNL-204188; FRBMEH; TRN: US200805%%337

Journal Information:: Free Radical Biology and Medicine, Vol. 37, Issue 3; ISSN 0891-5849

Country of Publication:: United States

Language:: English

References (31)

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99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
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Title: Oxidative DNA damage background estimated by a system model of base excision repair

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