William H. Strain

Inhibition of Walker 256 Carcinosarcoma Growth by Dietary Zinc Deficiency

Summary The zinc requirements of neoplastic growth were evaluated by comparing growth of a transplanted tumor (Walker 256 carcinosarcoma) in rats on a zinc-deficient diet with growth of this tumor in pair-fed or weight-matched controls. Rats receiving a zinc-deficient diet showed marked reduction of tumor growth and this was accompanied by a striking increase in survival. Rats in the pair-fed or weight-matched groups showed a slight reduction in tumor growth compared with ad libitum-fed controls but this caloric restriction did not increase survival. These results are consistent with a zinc requirement for tumor growth and suggest the need for study of clinical correlations between tumor growth rate and plasma zinc levels.

Mineral Element Correlation with Adenohypophyseal-Adrenal Cortex Function and Stress

A statistical correlationl was made between adrenocorticotropin (ACTH) and four elements in rats under control, stress, and stress-recovery conditions. Blood serum zinc showed a strong positive correlation with the rise in ACTH during stress and its decline in stress recovery. Serum calcium, copper, and magnesium demonstrated little correlation with ACTH changes. The strong ACTH-zinc correlation points to an as yet undefined interaction between ACTH and zinc

Trace elements that act to inhibit neoplastic growth.

Utah’s Mrs. John Doe runs far less risk of dying from breast cancer than the District of Columbia’s Mrs. Richard Roe. Similarly, lung cancer threatens John Doe much less than it does Richard Roe. Geographic variations in death rates from cancer in the United States have been well documented.’ The age-adjusted rate for cancer mortality per 100,000 of both sexes in 1960 was 153.4 in the District of Columbia, and 97.4 in Utah. New York ranked fourth with an age-adjusted rate of 143.5/100,000, and Ohio was thirteenth with a rate of 133.0/ 100,000. These large differences suggest that environmental factors may be the principal and preventable causes of cancer. Soil, water, and air are the obvious areas for investigation. In the past, considerable attention has been paid to trace substances which play causative roles in cancer but little effort has been expended to determine which elements may play protective roles. It is apparent from animal investigations that some of the trace elements inhibit experimental neoplastic growth. Iodine is perhaps the best known example. A deficient intake of iodine results in hyperplastic and, eventually, neoplastic changes in the thyroid gland. Adequate intake of iodine prevents these changes.? Similarly, other trace elements have recently been shown to have specific metabolic properties which may prevent, or can be utilized to inhibit, the growth of tumor. The mechanisms of action are not clear, and many of the reports require further substantiation.

Corticotropin dependency on zinc ions.

Summary The steroidogenic activity of corticotropin in rat adrenal slices in vitro has been studied with regard to the dependency of activity on zinc ion binding. Chelation of available zinc by diethyldithiocarbamate stopped the production of corticosterone, which was reversed by the addition of zinc. Corticotropin dependency on zinc ions is proposed, with the binding site of zinc being at the glutamate moiety, as suggested by thin layer chromatography.

Colorimetric determination of ACTH

Abstract A sensitive colorimetric method has been developed to measure changes of ACTH in pituitaries under control, stress and stress-recovery conditions. The method employs the quantification of the single tryptophan molecule contained in ACTH by means of the blue Schiffs base produced by p-dimethylaminobenzaldehyde. The method is sufficiently sensitive that ACTH may be determined directly in many stressful conditions rather than by cumbersome bioassay or radiolabeling procedures.

Arterial-Venous Magnesium Gradients in Hypovolemic Shock: An Indication of the Irreversible State

Summary Arterial-venous magnesium differences were examined in mongrel dogs stressed with reversible and lethal hypovolemia. Increases in serum Mg with hemorrhage have long been known to occur in both humans and animals, yet, increased blood Mg levels have not been viewed as an indicator of the irreversible shock state. The magnesium gradient was shown to be a good indicator of cell destruction which is consistent with lethal shock. This research was aided in part by support from the Steroid Research Fund, Cleveland, Ohio.