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[天然存在的氘的生物学意义:氘消耗的抗肿瘤作用]

[Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion].

作者信息

Somlyai Gábor, Molnár Miklós, Laskay Gábor, Szabó Mariann, Berkényi Tamás, Guller Imre, Kovács András

机构信息

HYD Rákkutató és Gyógyszerfejleszto Kft. Budapest Pf. 695 1539.

出版信息

Orv Hetil. 2010 Sep 5;151(36):1455-60. doi: 10.1556/OH.2010.28865.

DOI:10.1556/OH.2010.28865
PMID:20739263
Abstract

The concentration of deuterium is about 150 ppm (over 16 mmol/L) in surface water and more than 10 mmol/L in living organisms. Experiments with deuterium depleted water (30+/-5 ppm) revealed that due to D-depletion various tumorous cell lines (PC-3, human prostate, MDA, human breast, HT-29, human colon, M14, human melanoma) required longer time to multiply in vitro. DDW caused tumor regression in xenotransplanted mice (MDA and MCF-7, human breast, PC-3) and induced apoptosis in vitro and in vivo. Deuterium depleted water (25+/-5 ppm) induced complete or partial tumor regression in dogs and cats with spontaneous malignancies, it was registered as anticancer for veterinary use in 1999 (Vetera-DDW-25 A.U.V., 13/99 FVM). The hypodermic preparation of the registered veterinary drug was successfully tested in clinical investigations. Under the permission of the Hungarian Institute of Pharmacology (No. 5621/40/95) a randomized, double blind controlled, human Phase II clinical trial with prostate cancer was performed, in compliance with GCP principles, which exhibited a significant difference between the control and treated groups with respect to the examined parameters, median survival time and the extension of life-span. We suggest that cells are able to regulate the D/H ratio and the changes in the D/H ratio can trigger certain molecular mechanisms having a key role in cell cycle regulation. We suppose that not the shift in the intracellular pH, but the concomitant increase in the D/H ratio is the real trigger for the cells to enter into S phase. The decrease of D concentration can intervene in the signal transduction pathways thus leading to tumor regression. Deuterium depletion may open new perspectives in cancer treatment and prevention helping to increase the effectiveness of current oncotherapies.

摘要

地表水中氘的浓度约为150 ppm(超过16 mmol/L),而在生物体内则超过10 mmol/L。用贫氘水(30±5 ppm)进行的实验表明,由于氘的减少,各种肿瘤细胞系(PC-3,人前列腺癌;MDA,人乳腺癌;HT-29,人结肠癌;M14,人黑色素瘤)在体外增殖所需的时间更长。贫氘水导致异种移植小鼠(MDA和MCF-7,人乳腺癌;PC-3)的肿瘤消退,并在体外和体内诱导细胞凋亡。贫氘水(25±5 ppm)可使患有自发性恶性肿瘤的犬猫出现完全或部分肿瘤消退,1999年它被注册为兽用抗癌药(Vetera-DDW-25 A.U.V.,13/99 FVM)。已注册兽用药物的皮下制剂在临床研究中成功通过测试。在匈牙利药理研究所的许可下(编号5621/40/95),按照GCP原则进行了一项针对前列腺癌的随机、双盲对照人体II期临床试验,结果显示,在检查参数、中位生存时间和寿命延长方面,对照组和治疗组之间存在显著差异。我们认为细胞能够调节D/H比,D/H比的变化可以触发某些在细胞周期调节中起关键作用的分子机制。我们推测,真正促使细胞进入S期的不是细胞内pH值的变化,而是D/H比的同时增加。氘浓度的降低可以干预信号转导通路,从而导致肿瘤消退。氘的减少可能为癌症治疗和预防开辟新的前景,有助于提高当前肿瘤治疗的有效性。

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