Clinical Chemistry, Vol 21, 544-550, Copyright © 1975 by the American Association for Clinical Chemistry

Effect of Zinc Deficiency and Repletion on Thymidine Metabolism

¹ Biochemistry Research Laboratory, Veterans Administration Hospital, Baltimore, Md. 21218; and Department of Biochemical and Biophysical Sciences, The Johns Hopkins University, Baltimore, Md. 21205.

We studied the effect of zinc deficiency on thymidine metabolism in intact and wounded rats. Zinc deficiency was associated with significantly decreased incorporation of [methyl-³H]thymidine into skin DNA of both intact and wounded rats, as shown by liquid scintillation counting and autoradiography. With wounding, proliferation—as gauged by the labeling index—increased to about twice normal for zinc-supplemented rats, but 3.5-fold for zinc-deficient rats. However, despite the increased proliferation rate, wound-healing in deficient rats was always slower than in zinc-supplemented animals. Incorporation of ³H-labeled thymidine into spleen DNA at 2 and 4 h, and liver DNA at 4 h was also significantly less in zinc-deficient rats than in zinc-supplemented rats. Conversely, DNA synthesis was enhanced in the thymus gland of zinc-deficient rats. Further studies showed that significantly higher percentages of [methyl-¹⁴C]thymidine were oxidized by zinc-deficient rats. The specific involvement of the methyl group of thymidine was indicated by the observation of normal oxidations of [2-¹⁴C]thymidine. These findings support the view that zinc directly regulates DNA synthesis.

Submitted on October 16, 1974
Accepted on January 13, 1975