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Nucleic acid metabolism of a estrogen dependent adrenal cortical tumor Redman, Lyle Wharton

Abstract

The work in this thesis consisted of initial experiments designed to elucidate the role of hormones in a hormonal dependent tumor. Various aspects of nucleic acid synthesis in a hormone dependent tumor in the presence (growing) and absence (regressing) of the hormone were studied. The rates of nucleic acid synthesis were studied in whole animals by injecting radioactive formate and allowing the animal to incorporate radioactivity for various periods of time. Nucleic acids were extracted by PAS, phenol procedure and separated on a MAK column. Labelling of all species of nucleic acid was decreased in regressing tumors. In order to determine whether estrogen is acting directly on cells or at some indirect physiological level; the ability of cells from growing and regressing tumor to synthesize nucleic acids in vitro was determined. Results of experiments with these cell suspensions demonstrate that cells from the regressing tumor had a decreased ability to synthesize nucleic acids relative to growing tumor. The rate of DNA synthesis was decreased somewhat more than RNA. In preliminary experiments the activity of DNA dependent DNA polymerase and RNA polymerase from regressing tumor was compared with the same enzyme in growing tumor. The specific activity of both RNA and DNA polymerase was decreased in the regressing tumor. In target tissue like uterus stimulation with estradiol results in an increased rate of synthesis of several species of RNA. In the tumor system used in these preliminary experiments, stimulation with estrogens has a greater effect on the synthesis of DNA than RNA.

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