Measurement of Postreplicative DNA Metabolism and Damage in the Rodent Brain

Jay P. Patel; Mark L. Sowers; Jason L. Herring; Jacob A. Theruvathu; Mark R. Emmett; Bridget E. Hawkins; Kangling Zhang; Douglas S. Dewitt; Donald S. Prough; Lawrence C. Sowers

doi:10.1021/acs.chemrestox.5b00359

Measurement of Postreplicative DNA Metabolism and Damage in the Rodent Brain

Jay P. Patel, Mark L. Sowers, Jason L. Herring, Jacob A. Theruvathu, Mark R. Emmett, Bridget E. Hawkins, Kangling Zhang, Douglas S. Dewitt, Donald S. Prough, Lawrence C. Sowers

Pharmacology & Toxicology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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	https://doi.org/10.1021/acs.chemrestox.5b00359
State	Published - Dec 21 2015

ASJC Scopus subject areas

Toxicology

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10.1021/acs.chemrestox.5b00359

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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 R.; Hawkins, Bridget E.; Zhang, Kangling ; Dewitt, Douglas S.; Prough, Donald S.; Sowers, Lawrence C.

In: Chemical Research in Toxicology, Vol. 28, No. 12, 21.12.2015, p. 2352-2363.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Emmett, Mark R.

AU - Hawkins, Bridget E.

AU - Zhang, Kangling

AU - Dewitt, Douglas S.

AU - Prough, Donald S.

AU - Sowers, Lawrence C.

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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.

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Measurement of Postreplicative DNA Metabolism and Damage in the Rodent Brain

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