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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2003-01-0139. This Article Full Text (PDF) All Versions of this Article: 2003-01-0139v1 102/6/2068    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schwartz, G. N Articles by Gress, R. E Search for Related Content PubMed PubMed Citation Articles by Schwartz, G. N Articles by Gress, R. E Social Bookmarking                   What's this? Submitted January 15, 2003 Accepted May 10, 2003 Proliferation kinetics of subpopulations of human marrow cells determined by quantifying in vivo incorporation of [2H2]-glucose into DNA of S-phase cells Gretchen N Schwartz, Barbara A Vance, Benjamin M Levine, Motoharu Fukazawa, William G Telford, Denise Cesar, Marc Hellerstein, and Ronald E Gress* Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Department of Nutritional Sciences, University of California, Berkeley, CA, USA Hematopoietic-Associates, Wheaton, MD, USA Abramson Family Research Institute and Cancer Center, University of Pennsylvania, Philadelphia, PA, USA * Corresponding author; email: gressr{at}dc10a.nci.nih.gov. This report investigated in vivo turnover kinetics of marrow hematopoietic progenitors and precursors using a recently developed stable isotope-mass spectrometric technique (SIMST). Human subjects were administered a two day infusion of 6,6-[2H2]-glucose, a nontoxic stable isotope-labeled form of glucose, which becomes incorporated into DNA of all S-phase cells. The percent [2H2]-glucose incorporated into DNA in the form of [2H2]-deoxyadenosine (%[2H2]-dA enrichment) was determined by gas chromatography-mass spectrometry. The rate constant of replacement of unlabeled by labeled DNA strands (labeling kinetics) was used to calculate population turnover kinetics of CD34+ cells, CD133+ (i.e., CD133+) cells, and CD133-CD34+ cells. The observed mean replacement half life (t1/2) was 2.6 days for CD34+ cells, 2.5 days for CD133-CD34+ cells, and 6.2 days for CD133+ cells. Results from the estimated rate constant of replacement of labeled by unlabeled DNA (delabeling kinetics) also demonstrated slower turnover rates for AC133+ cells than for CD133-CD34+ cells. Although there was a relatively rapid initial decrease in the %[2H2]-dA enrichment, low levels of labeled DNA persisted in CD34+ cells for at least four weeks. The results indicate the presence of subpopulations of CD34+ cells with relatively rapid turnover rates and subpopulations with a slower t1/2 of 28 days. Results also demonstrate that in vivo [2H2]-glucose-SIMST is sensitive enough to detect differences in turnover kinetics between erythroid and megakaryocyte lineage cells. These studies are the first to demonstrate the use of in vivo [2H2]-glucose-SIMST to measure in vivo turnover kinetics of subpopulations of CD34+ cells and precursors in healthy human subjects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. A. Hsieh, C. M. Chai, and M. K. Hellerstein Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E965 - E972. [Abstract] [Full Text] [PDF]

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