Mechanisms of cytotoxic effects of heavy water (deuterium oxide: D20) on cancer cells

Takeda, Hiroshi; Nio, Yoshinori; Omori, Hiroshi; Uegaki, Ken; Hirahara, Noriyuki; Sasaki, Susumu; Tamura, Katsuhiro; Ohtani, Hiroki

doi:10.1097/00001813-199809000-00007

Cited by 40 publications

(35 citation statements)

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“…Even though excessive amounts of ingested D 2 O could be toxic to animals, the amount needed to cause a poisoning is so excessive it is considered non‐hazardous 15. In fact it has even been reported that D 2 O has potential as an anti‐cancer agent 40…”

Section: Resultsmentioning

confidence: 99%

Mechanical Investigations on Agar Gels Using Atomic Force Microscopy: Effect of Deuteration

Grant

Twigg

Savage

et al. 2011

Macro Materials & Eng

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The isotopic effect of exchanging deuterium with hydrogen on the mechanical and surface properties of agar gel is examined. The elastic modulus of the D2O gels obtained by AFM nanoindentation is significantly higher (factor of ≈1.5–2) than the modulus found in H2O agar gels. Furthermore, the modulus is independent of loading rate. Surface imaging reveals that the surface roughness gets progressively smaller with increasing agar concentration. All these data suggest that the isotopic replacement of deuterium enhances the mechanical properties of the agar gel, with significant advantages in its use as a biphasic scaffold.

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Section: Resultsmentioning

confidence: 99%

Mechanical Investigations on Agar Gels Using Atomic Force Microscopy: Effect of Deuteration

Grant

Twigg

Savage

et al. 2011

Macro Materials & Eng

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“…The impact of D 2 O on living organisms is of a considerable interest for biology and life sciences in general, both due to its documented lethal effects on higher organisms and particularly on those of the mammals [1][2][3][4][5], and to its possible curative potential through hampering proliferation of cancer cells [6][7][8][9][10][11]. This hampering effects and induction of apoptosis could be of a cytotoxic and/or a cytostatic nature, although neither well defined molecular targets of D 2 O, nor detailed mechanisms of such processes are clear.…”

Section: Introductionmentioning

confidence: 99%

Impact of D2O on peptidization of l-proline

Fulczyk

Łata

Talik

et al. 2019

Reac Kinet Mech Cat

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This is our follow-up study carried out in an order to collect experimental evidence regarding the impact of heavy water (D2O) on the spontaneous oscillatory peptidization of l-proline (l-Pro). Our earlier studies have been focused on the two sulfur-containing proteinogenic α-amino acids, i.e., l-cysteine (l-Cys) and l-methionine (l-Met), and it seemed interesting to assess the effect induced by D2O on one more proteinogenic α-amino acid, i.e., l-Pro. It needs to be added that unlike l-Met, but similar to l-Cys, the oscillatory peptidization of l-Pro dissolved in the organic-aqueous solvent characterizes with the circadian rhythm. As analytical techniques, we used high-performance liquid chromatography with the evaporative light-scattering detection (HPLC-ELSD), mass spectrometry (MS), scanning electron microscopy (SEM), and turbidimetry. The obtained results can in certain sense be viewed as analogous to those earlier reported for l-Cys and l-Met by demonstrating that heavy water considerably hampers the oscillatory peptidization of l-Pro. However, an unexpected observation was also made than unlike the cases with l-Cys and l-Met, the observed hampering effect of D2O on the oscillatory peptidization of l-Pro is not monotonously dependent on the concentration of D2O in the system, but it is the strongest pronounced for 10% (v/v) D2O in the employed binary methanol–water solvent (with the investigated proportions of D2O in this solvent changing from 0 to 30%). Although we have no rational explanation for this striking effect, we believe that it should not pass unnoticed and therefore it is emphasized in this study. Maybe this firm quantitative result will prove an inspiration for future researchers interested in getting a deeper insight into the role of D2O in life processes, and more specifically in the kinetic and the mechanistic aspects thereof.

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“…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]. Furthermore, several studies provided evidence for a significant reduction of human cancer cell lines growth in D 2 O culture medium [15], impairment of human tumor growth in animal models [16, 17], and generally a reduction of cellular proliferation at high deuterium concentrations in prokaryotic and eukaryotic cells [16, 18, 19]. …”

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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Mechanisms of cytotoxic effects of heavy water (deuterium oxide: D20) on cancer cells

Cited by 40 publications

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Mechanical Investigations on Agar Gels Using Atomic Force Microscopy: Effect of Deuteration

Mechanical Investigations on Agar Gels Using Atomic Force Microscopy: Effect of Deuteration

Impact of D2O on peptidization of l-proline

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

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