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Department of Nutrition, University of California, Davis, California 95616
Zinc deficiency during prenatal life results in a high incidence of gross malformations especially of CNS. Reduced 3H-thymidine incorporation into whole rat embryos has previously been reported in zinc deficient rats. The effect of zinc deficiency on regional DNA synthesis in the 12 day rat embryo was therefore investigated. Zinc deficiency was achieved by feeding normal pregnant rats a diet containing 0.4 ppm zinc from day 0 to day 12. Pair-fed controls received a diet containing 100 ppm zinc. Dams were injected with 3H-thymidine on day 12 and embryos removed 1 hour later. In embryos from zinc deficient dams, there was a lower incorporation of 3H-thymidine into DNA in the head regions than in comparable regions from ad libitum and pair-fed controls. Total DNA and RNA contents in the head and body regions of embryos from zinc deficient dams were lower than respective regions of pair-fed controls, but the greatest deficit occurred in the head region. Replacement of zinc 28 hours prior to injection of the label increased the low incorporation of 3H-thymidine/DNA in the head region of zinc deficient embryos. Autoradiographs of the head region indicated that reduced uptake of 3H-thymidine and reversal by zinc replacement occurred mainly in the developing CNS. These results demonstrate that the reduction in DNA synthesis resulting from zinc deficiency can be reversed by zinc alone, and that zinc deficiency in the mammalian system does not result in a general reduction in DNA synthesis in all tissues, but the head region is more vulnerable to reductions in zinc than the body region. The observation that DNA synthesis in the head region is reduced by zinc deficiency more than is the rest of the body may explain the increased vulnerability of the CNS to prenatal zinc deficiency.
KEY WORDS: zinc DNA embryonic CNS teratology
1 Supported in part by funds provided from the National Institutes of Health Postdoctoral Fellowship no. 1-F32 HD-05219-01 and National Institutes of Health Research Grant HD-01743.
Manuscript received 23 August 1976.