Effects of prolonged moderate body deuteration on proliferative activity in major cell renewal systems in mice

To evaluate the effects of prolonged moderate body deuteration on incorporation of tritiated thymidine (³HTdR) into the DNA of major cell renewal systems, young adult mice were given drinking fluid containing 30 % heavy water for 7, 14, 21, 42 and 70 days. Control mice drank tap water. Three hours prior to sacrifice, 925 kBq of ³HTdR were injected intravenously. Following extraction of the bulk of the soluble activity with an aqueous formalin solution, the residual ³H-activity of the organs was assayed by liquid scintillation counting and by autoradiography. The total thymic ³H-activity and the thymic weight, particularly of the cortex, were significantly reduced in deuterated mice early in the course of the experiment. The fraction of labeled thymocytes diminished to less than one half of the control values of day 70. The ³H-activity of the bone marrow in deuterated mice was reduced to about $\text{3}\text{4}$ of control values. In contrast, the total ³H-activity of the small intestine, as well as mean labeling index and mitotic index of small intestinal epithelia, were not markedly altered in deuterated versus control mice. Drinking water containing 30 % of heavy water did thus not result in generalized, profound and progressive disturbance of ³HTdR incorporation in all the major cell renewal systems in the mouse. The thymus and, to a lesser extent, the bone marrow, were unquestionably affected, but the depression of ³HTdR incorporation did not increase markedly in the course of 10 weeks. In these terms, the toxicity of 30 % heavy water in the drinking fluid appears minor. This is of particular interest since exposure to similar concentrations is known to elicit immunodepressive and/or antineoplastic effects.