Abstract
The DNA of all organisms is metabolically active due to persistent endogenous DNA damage, repair, and enzyme-mediated base modification pathways important for epigenetic reprogramming and antibody diversity. The free bases released from DNA either spontaneously or by base excision repair pathways constitute DNA metabolites in living tissues. In this study, we have synthesized and characterized the stable-isotope standards for a series of pyrimidines derived from the normal DNA bases by oxidation and deamination. We have used these standards to measure free bases in small molecule extracts from rat brain. Free bases are observed in extracts, consistent with both endogenous DNA damage and 5-methylcytosine demethylation pathways. The most abundant free base observed is uracil, and the potential sources of uracil are discussed. The free bases measured in tissue extracts constitute the end product of DNA metabolism and could be used to reveal metabolic disturbances in human disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2352-2363 |
| Number of pages | 12 |
| Journal | Chemical Research in Toxicology |
| Volume | 28 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 21 2015 |
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ASJC Scopus subject areas
- Toxicology
Cite this
Measurement of Postreplicative DNA Metabolism and Damage in the Rodent Brain. / Patel, Jay P.; Sowers, Mark L.; Herring, Jason L.; Theruvathu, Jacob A.; Emmett, Mark; Hawkins, Bridget; Zhang, Kangling; Dewitt, Douglas; Prough, Donald; Sowers, Lawrence.
In: Chemical Research in Toxicology, Vol. 28, No. 12, 21.12.2015, p. 2352-2363.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Measurement of Postreplicative DNA Metabolism and Damage in the Rodent Brain
AU - Patel, Jay P.
AU - Sowers, Mark L.
AU - Herring, Jason L.
AU - Theruvathu, Jacob A.
AU - Emmett, Mark
AU - Hawkins, Bridget
AU - Zhang, Kangling
AU - Dewitt, Douglas
AU - Prough, Donald
AU - Sowers, Lawrence
PY - 2015/12/21
Y1 - 2015/12/21
N2 - The DNA of all organisms is metabolically active due to persistent endogenous DNA damage, repair, and enzyme-mediated base modification pathways important for epigenetic reprogramming and antibody diversity. The free bases released from DNA either spontaneously or by base excision repair pathways constitute DNA metabolites in living tissues. In this study, we have synthesized and characterized the stable-isotope standards for a series of pyrimidines derived from the normal DNA bases by oxidation and deamination. We have used these standards to measure free bases in small molecule extracts from rat brain. Free bases are observed in extracts, consistent with both endogenous DNA damage and 5-methylcytosine demethylation pathways. The most abundant free base observed is uracil, and the potential sources of uracil are discussed. The free bases measured in tissue extracts constitute the end product of DNA metabolism and could be used to reveal metabolic disturbances in human disease.
AB - The DNA of all organisms is metabolically active due to persistent endogenous DNA damage, repair, and enzyme-mediated base modification pathways important for epigenetic reprogramming and antibody diversity. The free bases released from DNA either spontaneously or by base excision repair pathways constitute DNA metabolites in living tissues. In this study, we have synthesized and characterized the stable-isotope standards for a series of pyrimidines derived from the normal DNA bases by oxidation and deamination. We have used these standards to measure free bases in small molecule extracts from rat brain. Free bases are observed in extracts, consistent with both endogenous DNA damage and 5-methylcytosine demethylation pathways. The most abundant free base observed is uracil, and the potential sources of uracil are discussed. The free bases measured in tissue extracts constitute the end product of DNA metabolism and could be used to reveal metabolic disturbances in human disease.
UR - http://www.scopus.com/inward/record.url?scp=84951311163&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951311163&partnerID=8YFLogxK
U2 - 10.1021/acs.chemrestox.5b00359
DO - 10.1021/acs.chemrestox.5b00359
M3 - Article
VL - 28
SP - 2352
EP - 2363
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
SN - 0893-228X
IS - 12
ER -