[Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion].
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.
Somlyai
Gábor
G
HYD Rákkutató és Gyógyszerfejleszto Kft. Budapest Pf. 695 1539. gsomlyai@hyd.hu
Molnár
Miklós
M
Laskay
Gábor
G
Szabó
Mariann
M
Berkényi
Tamás
T
Guller
Imre
I
Kovács
András
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D002415:Cats; D045744:Cell Line, Tumor; D017322:Clinical Trials, Phase II as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy; D003903:Deuterium / Q000494:pharmacology*; D041961:Deuterium Exchange Measurement; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy; D016019:Survival Analysis; D013997:Time Factors; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D003903:Deuterium