Lucille S. Hurley

Influence of ashing techniques on the analysis of trace elements in animal tissue - I. Wet ashing

A multitude of methods exists at present for the solubilization of biological tissues for atomic absorption analysis. We have examined several common methods of wet ashing using NBS bovine liver in order to determine which acids, acid combinations, or bases should be used as digesting agents for accurate and precise measurement of iron, copper, zinc, and manganese. Nitric acid proved to be the most effective wet ashing agent. With nitric acid, mean concentrations for iron, copper, and zinc differed from NBS certified values by less than 1.5% while those for manganese differed by 4%.

Congenital Malformations Resulting from Zinc Deficiency in Rats.

Summary A mild but specific zinc deficiency was produced in female rats by the use of a purified diet lacking the element and by stringent elimination of sources of zinc contamination from the environment. Almost all of the full-term fetuses produced under such conditions showed gross congenital malformations encompassing a wide variety of organ systems, including skeletal, brain, eye, heart, lung, and urogenital defects. The fetuses from zinc-deficient females contained less zinc than did their controls, suggesting that the congenital anomalies resulted from a direct effect of lack of zinc in the fetal tissues.

Isolation of a low molecular weight zinc binding ligand from human milk

A low molecular weight zinc binding compound from human milk has been purified by ultrafiltration, gel filtration, and ion-exchange chromatography. Evidence is provided that this compound is citrate. A higher amount of citrate-bound zinc was found in human milk than in cows milk. It is suggested that the therapeutic value of human milk for patients with the genetic disorder of zinc metabolism acrodermatitis enteropathica (AE) derives from a greater content of bioavailable zinc citrate in human than in cows milk.

Zinc-Deficient Embryos: Reduced Thymidine Incorporation

The 12-day-old embryos of rats with a deficiency of zinc showed a reduced uptake of tritiated thymidine when compared with controls, as shown by liquid scintillation and autoradiography. The high incidence of gross congenital malformations resulting from zinc deficiency may thus be caused by DNA impaired DNA synthesis.

Teratogenic Effects of a Chelating Agent and Their Prevention by Zinc

Ingestion of a chelating agent (ethylenediaminetetraacetic acid) by female rats during pregnancy impaired reproduction and resulted in congenitally malformed young. When ethylenediaminetetraacetic acid was fed from days 6 to 21 of gestation, all of the full-term young had gross congenital malformations. These effects were prevented by simultaneous supplementation with 1000 parts per million of dietary zinc.

Neurological Defect: Manganese in Phenocopy and Prevention of a Genetic Abnormality of Inner Ear

A specific congenital ataxia may be caused by presence of mutant genes and by manganese deficiency during prenatal development in normal mice. Supplementation of the diet of mutant mice with manganese during prenatal development rectifies the aberrant development, resulting in normal behavior. The congential ataxa results from defective development of the the otoliths.

Calcium metabolism in manganese-deficient and zinc-deficient rats.

Summary The metabolism of calcium was studied in manganese-deficient and zinc-deficient rats by a method combining a kinetic study using 45Ca with a short-term classical balance study. There were no differences in managanese-deficient rats as compared with controls in any of the parameters of calcium metabolism, including pool size, endogenous fecal calcium, urinary clacium, or in the rates of calcium entering or leaving bone. The zinc-deficient animals, however, showed significant decreases, as compared with both ad libitum and restricted-intake controls, in a number of parameters of calcium metabolism. These included the rates of calcium entering and leaving bone, pool size, the rate of slow exhange, and the slowly exchangeable calcium in bone. The results suggest that the skeletal abnormals are not the result of abnormal calcium metabolism. In zinc deficiency, on the other hand, specific effects on calcium metabolism were noted. Thus it appears that zinc, but not manganese, is required for normal metabolism of calcium.

CONGENITAL MALFORMATIONS OF THE NERVOUS SYSTEM IN ZINC-DEFICIENT RATS

Publisher Summary This chapter discusses congenital malformations of the nervous system in zinc-deficient rats. Zinc deficiency appears to have a most marked effect on growing or proliferating tissues. Young weanling rats in a rapid stage of growth are severely affected by zinc deficiency and show extreme retardation or cessation of growth. Similarly, there is a complete arrest of ovarian maturation in the female and of spermatogenesis in the male. The deleterious effect of zinc deficiency on rapidly growing tissues is also very pronounced in the embryo. In an experiment described in the chapter, zinc deficiency in pregnant rats resulted in a high rate of embryonic death, severe intrauterine growth retardation, and a high incidence of congenital malformations affecting every organ system. In the experiment, rat embryos from zinc-deficient females showed a reduced uptake of tritiated thymidine when compared with controls, as measured by liquid scintillation and autoradiography.

Plasma zinc and leukocyte changes in weanling and pregnant rats during zinc deficiency.

Summary Dietary zinc deficiency was shown to result in a rapid fall in the plasma zinc levels of pregnant female and weanling male rats. In both groups, plasma zinc fell to 45-60% of its original level after only one day on the deficiency regime. Longer periods of zinc depletion (21 days) were found to increase the ratio of PMN leukocytes to lymphocytes in the blood by a factor of 10. General food restriction elicited a similar response in pregnant females but not in young males. The zinc deficiency regime had no effect upon the total leukocyte count or upon the concentration of zinc in the leukocytes.

Thymidine Kinase and DNA Polymerase Activity in Normal and Zinc Deficient Developing Rat Embryos

Summary Thymidine kinase and DNA polymerase activities were significantly (P < 0.05 and P < 0.01, respectively) lower in 9, 10, 11, and 12-day embryos taken from dams fed a zinc deficient diet than in those from ad libitum fed and restricted intake controls. An additional finding was that of increased activity of both thymidine kinase and DNA polymerase with increasing age of embryos. As previously found with thymidine kinase, addition of zinc and other divalent metal ions in vitro had little effect on restoration of DNA polymerase activity from zinc deficient extracts when added at concentrations of 0.01 and 0.05 mM. When added at a level of 0.2 mM, zinc, but not other metal ions, had an inhibitory effect on DNA polymerase activity. These findings support the hypothesis that the teratogenic effects of zinc deficiency are associated with the enzymes involved in DNA synthesis. This research was supported in part by NIH Research Grant No. HD-01743 from the National Institute of Child Health and Human Development.