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Dependence of the amplification factor on the body water deuterium enrichment.

Author information

Affiliations

  • 1. Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
      Authors
    • Şanal E 1
    (1 author)
  • 2. Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
      Authors
    • Drylewicz J 2
    • Tesselaar K 2
    • Borghans JAM 2
    (3 authors)
  • 3. Department of Infectious Disease, Imperial College London, London, United Kingdom.
      Authors
    • Asquith B 3
    (1 author)
  • 4. Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, Netherlands.
      Authors
    • de Boer RJ 4
    (1 author)

Journal of Immunological Methods, 02 Dec 2025, 546:114010
https://doi.org/10.1016/j.jim.2025.114010 PMID: 41344481 

Abstract 

Heavy water (D2O) labeling is the state-of-the-art technique to track the dynamics of circulating cells in vivo. D2O labels dividing cells through incorporation of deuterium into newly synthesized DNA, which is measured using GC/MS. The labeling rate depends on (1) the level of body water enrichment, (2) cell kinetics, and (3) an amplification factor quantifying the deoxyribose enrichment relative to the body water enrichment. This amplification factor is typically estimated using a reference population undergoing rapid turnover (such as granulocytes), and is larger than one because deoxyribose contains seven hydrogens that can be replaced by deuterium. In a meta-analysis, we found that individuals differ markedly in this amplification factor. Since the amplification factor also depends on the level of body water enrichment, we use conventional binomial expressions to describe the fractions of deoxyribose incorporating zero, one, two, or more deuterium atoms. We extend this classic binomial model with a new parameter, 0<γ<1, describing the relative contribution of hydrogens from body water during deoxyribose synthesis. While for most studies, our 'novel Binomial' model reasonably explains the slope with which the amplification factor declines with the level of body water enrichment, we find that some individual amplification factors differ considerably from their expected values Re-fitting deuterium labeling data of granulocytes with the Binomial model reveals that the actual decrease is steeper than expected. We speculate that this residual variation depends on differences in diet, metabolism, and/or life style, which apparently correlate with daily fluid intake.

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Read article at publisher's site: https://doi.org/10.1016/j.jim.2025.114010

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    Funding 

    Funders who supported this work.

    Blood Cancer UK (1)

    • Grant ID: 15012

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    Dutch Research Council (NWO) (1)

    • Grant ID: 09150181910016

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    EU Framework Programme for Research and Innovation Marie Skłodowska-Curie Actions (1)

    • Grant ID: 764698

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    European Commission

      Horizon 2020 Framework Programme

        Leukemia and Lymphoma Research

          Seventh Framework Programme (1)

          • Grant ID: 317040

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          Wellcome Trust (2)

          • Grant ID: 220794/Z/20/Z

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          • Grant ID: 103865Z/14/Z

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