Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water

Abstract Deuterated water (2H2O) is a label commonly used for safe quantitative measurement of deuterium enrichment into DNA of proliferating cells. More recently, it has been used for labeling proteins and other biomolecules. Our in vitro - in vivo research reports important stable isotopic labelin...

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Autores principales: Don E. Farthing, Nataliya P. Buxbaum, Philip J. Lucas, Natella Maglakelidze, Brittany Oliver, Jiun Wang, Kevin Hu, Ehydel Castro, Catherine V. Bare, Ronald E. Gress
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/d4a83883366a4094aed2ee20a95b6681
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spelling oai:doaj.org-article:d4a83883366a4094aed2ee20a95b66812021-12-02T16:06:25ZComparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water10.1038/s41598-017-04404-22045-2322https://doaj.org/article/d4a83883366a4094aed2ee20a95b66812017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04404-2https://doaj.org/toc/2045-2322Abstract Deuterated water (2H2O) is a label commonly used for safe quantitative measurement of deuterium enrichment into DNA of proliferating cells. More recently, it has been used for labeling proteins and other biomolecules. Our in vitro - in vivo research reports important stable isotopic labeling enrichment differences into the DNA nucleosides and their isotopologues (e.g. deoxyadenosine (dA) M + 1, dA M + 2, dA M + 3), as well as tumor cell proliferation effects for various forms of commercially available stable heavy water (2H2O, H2 18O, and 2H2 18O). Using an in vitro mouse thymus tumor cell line, we determined that H2 18O provides superior DNA labeling enrichment quantitation, as measured by GC-positive chemical ionization (PCI)-MS/MS. In addition, at higher but physiologically relevant doses, both 2H2 18O and 2H2O down modulated mouse thymus tumor cell proliferation, whereas H2 18O water had no observable effects on cell proliferation. The in vivo labeling studies, where normal mouse bone marrow cells (i.e. high turnover) were evaluated post labeling, demonstrated DNA enrichments concordant with measurements from the in vitro studies. Our research also reports a headspace-GC-NCI-MS method, which rapidly and quantitatively measures stable heavy water levels in total body water.Don E. FarthingNataliya P. BuxbaumPhilip J. LucasNatella MaglakelidzeBrittany OliverJiun WangKevin HuEhydel CastroCatherine V. BareRonald E. GressNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Don E. Farthing
Nataliya P. Buxbaum
Philip J. Lucas
Natella Maglakelidze
Brittany Oliver
Jiun Wang
Kevin Hu
Ehydel Castro
Catherine V. Bare
Ronald E. Gress
Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water
description Abstract Deuterated water (2H2O) is a label commonly used for safe quantitative measurement of deuterium enrichment into DNA of proliferating cells. More recently, it has been used for labeling proteins and other biomolecules. Our in vitro - in vivo research reports important stable isotopic labeling enrichment differences into the DNA nucleosides and their isotopologues (e.g. deoxyadenosine (dA) M + 1, dA M + 2, dA M + 3), as well as tumor cell proliferation effects for various forms of commercially available stable heavy water (2H2O, H2 18O, and 2H2 18O). Using an in vitro mouse thymus tumor cell line, we determined that H2 18O provides superior DNA labeling enrichment quantitation, as measured by GC-positive chemical ionization (PCI)-MS/MS. In addition, at higher but physiologically relevant doses, both 2H2 18O and 2H2O down modulated mouse thymus tumor cell proliferation, whereas H2 18O water had no observable effects on cell proliferation. The in vivo labeling studies, where normal mouse bone marrow cells (i.e. high turnover) were evaluated post labeling, demonstrated DNA enrichments concordant with measurements from the in vitro studies. Our research also reports a headspace-GC-NCI-MS method, which rapidly and quantitatively measures stable heavy water levels in total body water.
format article
author Don E. Farthing
Nataliya P. Buxbaum
Philip J. Lucas
Natella Maglakelidze
Brittany Oliver
Jiun Wang
Kevin Hu
Ehydel Castro
Catherine V. Bare
Ronald E. Gress
author_facet Don E. Farthing
Nataliya P. Buxbaum
Philip J. Lucas
Natella Maglakelidze
Brittany Oliver
Jiun Wang
Kevin Hu
Ehydel Castro
Catherine V. Bare
Ronald E. Gress
author_sort Don E. Farthing
title Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water
title_short Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water
title_full Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water
title_fullStr Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water
title_full_unstemmed Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water
title_sort comparing dna enrichment of proliferating cells following administration of different stable isotopes of heavy water
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/d4a83883366a4094aed2ee20a95b6681
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