Hydantoin derivative formation from oxidation of 7,8-dihydro-8-oxo- 2′-deoxyguanosine (8-oxodG) and incorporation of 14C-labeled 8-oxodG into the DNA of human breast cancer cells

Soo Hah Sang, Hyung M. Kim, Rhoda A. Sumbad, Paul Henderson

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

One-electron oxidation of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) yielded a guanidinohydantoin derivative (dGh) and a spiroiminodihydantoin derivative (dSp), both putatively mutagenic products that may be formed in vivo. The nucleoside dGh was the major product at room temperature, regardless of pH. The results are contrary to previously published model studies using 2′,3′,5′-triacetoxy-8-oxo-7,8- dihydroguanosine (Luo, W.; Miller, J. G.; Rachlin, E. M.; Burrows, C. J. Org. Lett. 2000, 2, 613; Luo, W.; Miller, J.G.; Rachlin, E.M.; Burrows, C.J. Chem. Res. Toxicol. 2001, 14, 927), who observed a spiroiminodihydantoin derivative as the major product at neutral pH. Clearly, the functional groups attached to the ribose moiety of 8-oxodG influence the oxidation chemistry of the nucleobase derivative. To explore this chemistry in vivo, 14C-labeled 8-oxodG was synthesized and incubated with growing MCF-7 human breast cancer cells, resulting in the incorporation of the compound into cellular DNA as measured by a novel accelerator mass spectrometry assay.

Original languageEnglish (US)
Pages (from-to)3627-3631
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number15
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

Hydantoins
Cells
Breast Neoplasms
Derivatives
Oxidation
DNA
Ribose
Nucleosides
Mass Spectrometry
Electrons
Functional groups
Particle accelerators
Mass spectrometry
Assays
Temperature
8-oxo-7-hydrodeoxyguanosine
spiroiminodihydantoin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

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title = "Hydantoin derivative formation from oxidation of 7,8-dihydro-8-oxo- 2′-deoxyguanosine (8-oxodG) and incorporation of 14C-labeled 8-oxodG into the DNA of human breast cancer cells",
abstract = "One-electron oxidation of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) yielded a guanidinohydantoin derivative (dGh) and a spiroiminodihydantoin derivative (dSp), both putatively mutagenic products that may be formed in vivo. The nucleoside dGh was the major product at room temperature, regardless of pH. The results are contrary to previously published model studies using 2′,3′,5′-triacetoxy-8-oxo-7,8- dihydroguanosine (Luo, W.; Miller, J. G.; Rachlin, E. M.; Burrows, C. J. Org. Lett. 2000, 2, 613; Luo, W.; Miller, J.G.; Rachlin, E.M.; Burrows, C.J. Chem. Res. Toxicol. 2001, 14, 927), who observed a spiroiminodihydantoin derivative as the major product at neutral pH. Clearly, the functional groups attached to the ribose moiety of 8-oxodG influence the oxidation chemistry of the nucleobase derivative. To explore this chemistry in vivo, 14C-labeled 8-oxodG was synthesized and incubated with growing MCF-7 human breast cancer cells, resulting in the incorporation of the compound into cellular DNA as measured by a novel accelerator mass spectrometry assay.",
author = "Sang, {Soo Hah} and Kim, {Hyung M.} and Sumbad, {Rhoda A.} and Paul Henderson",
year = "2005",
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T1 - Hydantoin derivative formation from oxidation of 7,8-dihydro-8-oxo- 2′-deoxyguanosine (8-oxodG) and incorporation of 14C-labeled 8-oxodG into the DNA of human breast cancer cells

AU - Sang, Soo Hah

AU - Kim, Hyung M.

AU - Sumbad, Rhoda A.

AU - Henderson, Paul

PY - 2005/8/1

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AB - One-electron oxidation of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) yielded a guanidinohydantoin derivative (dGh) and a spiroiminodihydantoin derivative (dSp), both putatively mutagenic products that may be formed in vivo. The nucleoside dGh was the major product at room temperature, regardless of pH. The results are contrary to previously published model studies using 2′,3′,5′-triacetoxy-8-oxo-7,8- dihydroguanosine (Luo, W.; Miller, J. G.; Rachlin, E. M.; Burrows, C. J. Org. Lett. 2000, 2, 613; Luo, W.; Miller, J.G.; Rachlin, E.M.; Burrows, C.J. Chem. Res. Toxicol. 2001, 14, 927), who observed a spiroiminodihydantoin derivative as the major product at neutral pH. Clearly, the functional groups attached to the ribose moiety of 8-oxodG influence the oxidation chemistry of the nucleobase derivative. To explore this chemistry in vivo, 14C-labeled 8-oxodG was synthesized and incubated with growing MCF-7 human breast cancer cells, resulting in the incorporation of the compound into cellular DNA as measured by a novel accelerator mass spectrometry assay.

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