Pathologisch-Anatomische Veränderungen bei Subakuter Deuteriumoxydvergiftung von Mäusen

Dybing, Ottar; Guldberg, Gustav; Hansen, Klaus

doi:10.1007/bf01777243

Cited by 6 publications

(5 citation statements)

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“…However, it is known for decades that D 2 O directly interferes with the cell cycle, markedly slows down the overall gene expression, and reduces the proliferation of various cell types, which has proven a possibility to impair human tumor growth in animal models. [1][2][3][4][5][6][7] D 2 O is the only known chemical substance that affects the period of circadian oscillations, consistently increasing the length of each cycle. [8] Generally, heavy water or deuterium oxide (D 2 O) is a form of water, where both protium atoms ( 1 H-only one proton) of normal H 2 O are replaced by the hydrogen isotope deuterium ( 2 H-one proton + one neutron).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

et al. 2021

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Solvent conditions are unexpectedly sufficient to drastically and reversibly slow down cells. In vitro on the molecular level, protein–solvent interactions drastically change in the presence of heavy water (D2O) and its stronger hydrogen bonds. Adding D2O to the cell medium of living cells increases the molecular intracellular viscosity. While cell morphology and phenotype remain unchanged, cellular dynamics transform into slow motion in a changeable manner. This is exemplified in the slowdown of cell proliferation and migration, which is caused by a reversible gelation of the cytoplasm. In analogy to the time–temperature superposition principle, where temperature is replaced by D2O, an increase in viscosity slows down the effective time. Actin networks, crucial structures in the cytoplasm, switch from a power‐law‐like viscoelastic to a more rubber‐like elastic behavior. The resulting intracellular resistance and dissipation impair cell movement. Since cells are highly adaptive non‐equilibrium systems, they usually respond irreversibly from a thermodynamic perspective. D2O induced changes, however, are fully reversible and their effects are independent of signaling as well as expression. The stronger hydrogen bonds lead to glass‐like, drawn‐out intramolecular dynamics, which may facilitate longer storage times of biological matter, for instance, during transport of organ transplants.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

et al. 2021

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“…Furthermore, the (partial) inhibition of protein expression as well as protein misfolding could trigger apoptosis or hamper cell growth and division. Although previous studies characterized the toxicity of deuterium oxide in animals [ 10 – 12 ] by causing severe damages to specific organs such as the mouse kidney [ 10 ], deuterium oxide is still believed to have potential as an antiproliferative agent. While deuterium oxide at concentrations greater than 20% of body weight is highly toxic to animals [ 13 ], low concentrations of deuterium oxide seem to be harmless for animals and humans, and deuterated intraocular dyes are considered to be safe for clinical use [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Heavy Water Reduces GFP Expression in Prokaryotic Cell-Free Assays at the Translation Level While Stimulating Its Transcription

Hohlefelder

Stögbauer

Opitz

et al. 2013

BioMed Research International

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The in vitro proliferation of prokaryotic and eukaryotic cells is remarkably hampered in the presence of heavy water (D2O). Impairment of gene expression at the transcription or translation level can be the base for this effect. However, insights into the underlying mechanisms are lacking. Here, we employ a cell-free expression system for the quantitative analysis of the effect of increasing percentages of D2O on the kinetics of in-vitro GFP expression. Experiments are designed to discriminate the rates of transcription, translation, and protein folding using pDNA and mRNA vectors, respectively. We find that D2O significantly stimulates GFP expression at the transcription level but acts as a suppressor at translation and maturation (folding) in a linear dose-dependent manner. At a D2O concentration of 60%, the GFP expression rate was reduced to 40% of an undisturbed sample. We observed a similar inhibition of GFP expression by D2O in a recombinant Escherichia coli strain, although the inhibitory effect is less pronounced. These results demonstrate the suitability of cell-free systems for quantifying the impact of heavy water on gene expression and establish a platform to further assess the potential therapeutic use of heavy water as antiproliferative agent.

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“…At high deuterium concentrations such kinetic isotope effects slow down all metabolic processes, and consequently only very few reports on the cultivation of microorganisms in highly deuterated media are available from the literature [ 20 – 23 ]. For eukaryotes high deuterium oxide concentrations are even toxic, e.g., in mice intoxication with deuterium oxide resulted in degenerative defects on multiple organs [ 24 ]. Our current research on terpene biosynthesis using stable isotope labellings prompted us to investigate whether it is possible to obtain a fully deuterated terpene by culturing a bacterium in a 100% deuterated medium.…”

Section: Introductionmentioning

confidence: 99%

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

Citron¹,

Dickschat²

2013

Beilstein J. Org. Chem.

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SummaryDuring growth on fully deuterated medium the volatile terpene [2H26]-1-epi-cubenol was released by the actinomycete Streptomyces griseus. This compound represents the first completely deuterated terpene obtained by fermentation. Despite a few previous reports in the literature the operability of this approach to fully deuterated compounds is still surprising, because the strong kinetic isotope effect of deuterium is known to slow down all metabolic processes in living organisms. Potential applications of completely labelled compounds from natural sources in structure elucidation, biosynthetic or pharmacokinetic investigations are discussed.

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Pathologisch-Anatomische Veränderungen bei Subakuter Deuteriumoxydvergiftung von Mäusen

Cited by 6 publications

References 1 publication

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

Heavy Water Reduces GFP Expression in Prokaryotic Cell-Free Assays at the Translation Level While Stimulating Its Transcription

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

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Pathologisch-Anatomische Veränderungen bei Subakuter Deuteriumoxydvergiftung von Mäusen

Cited by 6 publications

References 1 publication

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

Heavy Water Reduces GFP Expression in Prokaryotic Cell-Free Assays at the Translation Level While Stimulating Its Transcription

[2H26]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

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[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus