The Role of Endogenous Versus Exogenous DNA Damage in Risk Assessment

James Swenberg, Yongquan Lai, Rui Yu, Vyom Sharma, Benjamin Moeller, Hadley Hartwell, Jacqueline Gibson, Jun Nakamura

Research output: Chapter in Book/Report/Conference proceedingChapter


The role of endogenous versus exogenous DNA damage in genotoxicity and carcinogenesis is reviewed from recent publications on genotoxicity, focusing on low-dose effects and risk assessment. Data for aldehydes, alkylating agents, oxidative stress, and radiation are summarized, with particular emphasis on new approaches that provide quantitative data on endogenous DNA damage and mutagenesis. Such data have markedly improved with new analytical instrumentation, such as mass spectrometry. A major breakthrough in these techniques has been the incorporation of stable isotope exposures, so that exogenous DNA damage can be readily distinguished from endogenous DNA damage. This has greatly improved both the accuracy of the data and our knowledge. Such data lend themselves to the development of new approaches for science-based risk assessment. As these new approaches advance, it should be possible to make science-based risk assessments for genotoxic agents, rather than resorting to the default-driven approaches that have no scientific basis.

Original languageEnglish (US)
Title of host publicationThresholds of Genotoxic Carcinogens
Subtitle of host publicationFrom Mechanisms to Regulation
PublisherElsevier Inc.
Number of pages20
ISBN (Print)9780128016633
StatePublished - May 25 2016
Externally publishedYes


  • DNA damage
  • Endogenous exposome
  • Mutagenesis
  • Risk assessment
  • Stable isotopes

ASJC Scopus subject areas

  • Medicine(all)


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