Protection of Mice from Whole-Body Gamma Radiation by Deuteration of Drinking Water

Laissue, Jean A.; Bally, E; Joel, D. D.; Slatkin, D.N.; Stoner, Richard D.

doi:10.2307/3576164

Cited by 16 publications

(14 citation statements)

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“…Moderate deuteration of body fluids does not affect body weight, life span or behavior of normal mice (Laissue et al, 1987). However, heavy water enhances the effects of BLM on xenotransplanted human neoplasms in nude mice (Altermatt et al, 1990).…”

Section: H Ld M-h M-d H-hmentioning

confidence: 99%

“…Thus, BLM-induced lung toxicity was enhanced by simultaneous or preceding irradiation of the lung (Samuels et al, 1976), presumably via generation of additional free radicals by ionizing radiation (Dormandy, 1983). Moderate body deuteration of mice by ingestion of heavy water is radioprotective (Laissue et al, 1987). This is probably due to deuterium-induced modification of physicochemical factors such as radiolysis of water, yield of ions, free radicals and molecular singlet oxygen (Fielden and Hart, 1968;Merkel et al, 1972).…”

Section: Histological Evaluationmentioning

confidence: 99%

“…Partial deuteration of mice by ingestion of heavy water prior to irradiation lessens their susceptibility to lethal doses of whole-body gamma irradiation (Laissue et al, 1987). The radioprotective effects of heavy water are deemed to be related to the presence of deuterium in body fluids (Laissue et al, 1987). It is conceivable that deuterium, enriched in body fluids, acts as a scavenger of free radicals.…”

mentioning

confidence: 99%

“…In addition, the prophylactic use of anti-oxidants might reduce lung damage: for instance, scavengers of lipid peroxide radicals have been shown to inhibit BLM-induced lipid peroxidation in vitro (Ekimoto et al, 1985). Partial deuteration of mice by ingestion of heavy water prior to irradiation lessens their susceptibility to lethal doses of whole-body gamma irradiation (Laissue et al, 1987). The radioprotective effects of heavy water are deemed to be related to the presence of deuterium in body fluids (Laissue et al, 1987).…”

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confidence: 99%

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Paradoxical effects of bleomycin and heavy water (D₂O) in mice

Gaeng¹,

Geiser²,

Cruz‐Orive³

et al. 1995

Intl Journal of Cancer

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Bleomycin (BLM) lacks many side effects of other cytostatic drugs. Pulmonary toxicity is the major dose-limiting effect of BLM. This is based in part on generation of free radicals. It is conceivable that deuterium in body fluids lessens the production of free radicals, thus preventing or diminishing the morphologic expression of pulmonary BLM toxicity. We therefore studied the effect of moderate deuteration of body fluids on BLM-induced lung damage in BALB/c-mice. In addition to conventional histopathological methods, we used a vertical sectioning design for stereological estimation of pulmonary volumes and surface areas. BLM (low/medium/high dose: 25/50/75 IU/kg body weight) was injected i.p. once a week for 6 weeks. Half the mice drank deuterated water before, during and after BLM treatment. Three weeks after the last injection, the lungs were fixed by airway instillation. Deuterated animals treated with BLM lacked signs of irreversible BLM-induced pulmonary damage. Conversely, focal sub-pleural fibrosis and fibrosing alveolitis were present in BLM-treated mice drinking tap water. Deuterated mice had stereological values for almost all lung parameters that were lower than in non-deuterated mice. The organ-specific advantage of deuteration was offset by marked enhancement of systemic toxicity of BLM. We conclude that (1) moderate concentrations of deuterium may prevent the development of fibrosing alveolitis in BLM-treated mice, possibly by reducing proliferation of alveolar fibroblasts, and, less probably, by impairing generation or enhancing capture of free radicals; (2) the toxicity of BLM was enhanced by ingestion of deuterium, resulting in morphological liver alterations and increased mortality.

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Section: H Ld M-h M-d H-hmentioning

confidence: 99%

Section: Histological Evaluationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Paradoxical effects of bleomycin and heavy water (D₂O) in mice

Gaeng¹,

Geiser²,

Cruz‐Orive³

et al. 1995

Intl Journal of Cancer

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“…in biological systems, the effect of replacing hydrogen with deuterium has also been well documented (7,8). early studies revealed that the life span of mice with ascites tumors was prolonged by drinking 25-30% deuterium water (deuterated water) (9), and the mortality caused by 60 co irradiation in mice was significantly decreased by drinking 30% deuterated water (10). Gross and Spindel discovered that high concentrations of deuterium in water induced stagnation mitosis (11).…”

Section: Introductionmentioning

confidence: 99%

Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis

Cong

Zhang²,

Sheng³

et al. 2010

Experimental and Therapeutic Medicine

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Abstract. to investigate the in vivo and in vitro inhibitory effects of deuterium-depleted water (ddW) on human lung cancer and the possible mechanisms underlying these effects, we cultured and treated human lung carcinoma cell line A549 and human embryonic lung fibroblasts HLF-1 with various concentrations of ddW from 2 to 72 h. cellular growth inhibition rates were determined using the 3-(4, 5-dimethyldiazol-2-yl)-2, 5-diphenyltetrazolium-bromide) (mtt) proliferation assay. a549 cells were treated with 50±5 ppm ddW, and the morphology and structure of cells were observed by scanning electron microscopy (Sem). We observed alterations in the cellular skeleton by transmission electron microscopy (tem) and changes in cell cycle by flow cytometry. Our data showed that DDW significantly inhibited the proliferation of A549 cells at a specific time point, and cells demonstrated the characteristic morphological changes of apoptosis under Sem and tem. the length of the S phase increased significantly in cells treated with 50 ppm ddW, whereas the G0 to G1 phase and G2 to m phase were decreased. We observed ddW-induced cellular apoptosis using terminal deoxynucleotidyl transferase dutp nick end labeling (tunel) and dna fragment analyses. in addition, we established a tumor transplantion model by injecting h460 tumor cells into subcutaneous tissue of BalB/c mice treated with ddW for 60 days. We determined the tumor inhibition rate of treated and control groups and found that the tumor weight was significantly decreased and the tumor inhibition rate was approximately 30% in the ddW group. We conclude that ddW is a promising new anticancer agent with potential for future clinical application. Introductionlung cancer is one of the leading causes of death by cancer worldwide; approximately 80% of lung cancers can be histologically classified as non-small cell lung cancers (nSclcs). most patients present with locally advanced (37%) or metastatic (38%) disease at the time of diagnosis (1). despite advances in chemotherapy, the average 5-year survival rate for patients with advanced nSclc remains extremely poor (2), thus new agents are needed to establish an effective therapeutic strategy against nSclc. there is great interest in developing new preventive and anti-tumor agents that are more effective and less toxic. it has recently been suggested that deuterium-depleted water (ddW) may play a potentially beneficial role in cancer prevention (3).in nature, the ratio between deuterium and hydrogen (d/h) in ordinary water is approximately 1:6600 (4). it has been known for decades that the mass difference between hydrogen and deuterium leads to differences in the physical and chemical behavior of the two stable isotopes (5,6). in biological systems, the effect of replacing hydrogen with deuterium has also been well documented (7,8). early studies revealed that the life span of mice with ascites tumors was prolonged by drinking 25-30% deuterium water (deuterated water) (9), and the mortality caused by 60 co irradiation in mice was sig...

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Heavy water enhances the antineoplastic effect of 5‐fluoro‐uracil and bleomycin in nude mice bearing human carcinoma

Altermatt

Gebbers

Laissue

1990

Intl Journal of Cancer

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The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.

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Protection of Mice from Whole-Body Gamma Radiation by Deuteration of Drinking Water

Cited by 16 publications

References 5 publications

Paradoxical effects of bleomycin and heavy water (D₂O) in mice

Paradoxical effects of bleomycin and heavy water (D₂O) in mice

Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis

Heavy water enhances the antineoplastic effect of 5‐fluoro‐uracil and bleomycin in nude mice bearing human carcinoma

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Protection of Mice from Whole-Body Gamma Radiation by Deuteration of Drinking Water

Cited by 16 publications

References 5 publications

Paradoxical effects of bleomycin and heavy water (D2O) in mice

Paradoxical effects of bleomycin and heavy water (D2O) in mice

Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis

Heavy water enhances the antineoplastic effect of 5‐fluoro‐uracil and bleomycin in nude mice bearing human carcinoma

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Product

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Paradoxical effects of bleomycin and heavy water (D₂O) in mice

Paradoxical effects of bleomycin and heavy water (D₂O) in mice