The endogenous exposome.
The concept of the Exposome is a compilation of diseases and one's lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the endogenous exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions.
University of North Carolina, Chapel Hill, NC, United States.
Jun
J
Nakamura
University of North Carolina, Chapel Hill, NC, United States.
Esra
E
Mutlu
University of North Carolina, Chapel Hill, NC, United States.
Vyom
V
Sharma
University of North Carolina, Chapel Hill, NC, United States.
Leonard
L
Collins
University of North Carolina, Chapel Hill, NC, United States.
Wanda
W
Bodnar
University of North Carolina, Chapel Hill, NC, United States.
Rui
R
Yu
University of North Carolina, Chapel Hill, NC, United States.
Yongquan
Y
Lai
University of North Carolina, Chapel Hill, NC, United States; Lovelace Respiratory Research Institute, Albuquerque, NM, United States.
Benjamin
B
Moeller
University of North Carolina, Chapel Hill, NC, United States.
Kun
K
Lu
University of North Carolina, Chapel Hill, NC, United States. Electronic address: jswenber@email.unc.edu.
James
J
Swenberg
D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics*; D018736:DNA Adducts / Q000187:drug effects / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D007553:Isotope Labeling; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics*
D018736:DNA Adducts
DNA damage; Endogenous exposome; Mutagenesis; Risk assessment; Stable isotopes