Schweres Wasser (D₂O)hemmt das Wachstum menschlicher xenotransplantierter oropharyngealer Karzinome

Zusammenfassung

Deuterium (D, ²H), das natürliche, stabile, schwere Isotop des Wasserstoffs führt als schweres Wasser (Deuteriumoxid, D₂O) zu mannigfaltigen biologischen Effekten. Es ist unter anderem eine wachstumshemmende Wirkung auf Mäuseneoplasmen nachgewiesen worden. Wir haben diese Wirkung auf menschliche, in thymusdysplastische nackte Mäuse transplantierte oropharyngeale Karzinome untersucht. Eine mittelgradige Deuterierung des Körperwassers (≤ 20 Atom%) der Versuchstiere führte zu einer bemerkenswerten Wachstumshemmung der Karzinome; der Effekt scheint umgekehrt proportional dem Differenzierungsgrad und der Wachstumsrate der Karzinome zu sein. Histologisch fanden wir keine Unterschiede zwischen Spendertumoren und den in nackten Mäusen gewachsenen Tumortransplantaten behandelter oder unbehandelter Tiere.

Summary

The large mass ratio of D to H, 2 to 1, gives rise to multiple effects in living organisms, when D is administered as heavy water (D₂O). Deuterium at high concentration interferes with cell division and depresses the uptake of DNA-precursors in mammalian cells (Katz et al., 1970). However, the effects of D₂O on the organism disappear after cessation of deuteration of the body water. Mammals do not survive more than 35% of D₂0 substitution for normal water in their body fluids for long periods of time. However, mice drinking 30% D₂O have a normal life span and normal body weight (Katz et al., 1970; Hodel et al., 1982). Heavy water also exerts antineoplastic effects. We demonstrated that moderate body deuteration combined with a cytostatic drug significantly increases the survival time of mice bearing transplantable murine neoplasms (Laissue et al., 1982). Hitherto, it is not known whether heavy water affects human neoplasms in the same way. Therefore, we have studied human squamous cell carcinomas of the oropharyngeal region which were xenografted in nude mice. A moderate deuteration of body water of the mice (≤ 20 atom%) drinking 30% D₂O, inhibited the tumour growth markedly by a factor of 0.4 to 0.5 compared to the growth of the same tumours in control animals drinking tap water (Fig. 1, 2). This effect of D₂O seems to be directly proportional to the grade of malignancy of the carcinomas. Histologically, no differences were detectable between the original carcinomas and the tumour grafts in animals with and without D₂O (Fig. 3).