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The effects of tumor on the nucleic acid metabolism of the host tissues Nixon, John Charles

Abstract

A humoral factor elaborated by tumor tissue has been suggested as the etiological agent which causes the systemic effects accompanying malignant disease. Because of the important role of the nucleic acids in the metabolism of the cell, it was postulated that the tumor factor might produce the systemic effects by altering the nucleic acid metabolism of the host tissues. With these considerations in mind, a study has been made of the effect of several transplantable tumors on the incorporation of formate-C¹⁴ and tritiated thymidine into the nucleic acids of the host tissues. Studies on the incorporation of thymidine into the host tissues have been emphasized since this compound is a specific precursor of DNA thymine. Liquid scintillation counting methods were developed in order to assay the radioactivity of the tritium-labelled thymine. Methods for the liquid scintillation counting of carbon-¹⁴ labelled purines and pyrimidines were also established. The presence of the ascitic and subcutaneous forms of the Ehrlich tumor was found to have little effect on the incorporation of formate-C¹⁴ into the nucleic acids of the host tissues. In contrast an increased uptake of tritiated thymidine by the DNA of the host tissues was observed in animals bearing the Ehrlich ascites tumor, Novikoff hepatoma and the Walker 256 carcinosarcoma. This effect was particularly striking in the case of the liver and spleen of animals bearing the Walker 256 tumor. Other investigators have isolated a substance known as toxohormone from tumor tissue which has been shown to produce certain systemic effects similar to those of tumor tissue. It was postulated that the increased incorporation of thymidine into the DNA of the host tissues might be the result of the action of toxohormone. In order to test this hypothesis, the effect of toxohormone on the incorporation of tritiated thymidine into the DNA of rat liver and spleen was studied. Crude toxohormone caused an increased uptake of thymidine by the DNA of spleen, but the results obtained for liver were equivocal. A highly purified fraction of toxohormone was prepared by ion-exchange chromatography and gel filtration. However this fraction had no effect on the incorporation of thymidine into the DNA of rat liver and spleen. These results suggested that tumor tissue might contain a factor which stimulates DNA synthesis and which could be isolated in company with crude toxohormone.

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