Biochemical investigations on cellular proliferation

Abstract

The investigations described here were begun at the suggestion of Professor G. F. Marrian and. Professor J. R. Learmonth to examine the relationship between ribonucleic acids (and their derivatives) and the processes of tissue growth (including wound healing).Examination of the literature suggested that ribonucleic acid derivatives might be present in rapidly growing tissues, be released by livin `. cells on injury, and be present in the growth -promoting factors of embryo juice. The investigation falls into three parts. In Part I the growth promoting properties of various siubstances, including ribonucleic acid derivatives, are investigated with the aid of a tissue culture test. In Part II the question of the release of such compounds b7 injured cells is examined. In Part III the ribonucleic content of tissues, especially rapidly growing tissues, is dealt with.The results of this investigation have confirmed the view that no other substances can stimulate the growth of tissues in vitro so successfully as do extracts of embryonic tissue. It is improbable. however, that the effects of embryo extract can be attributed to any one individual constituent. Attempts to separate any particular constituent, or group of constituents, have always resulted in loss of activity. Wile embryo extracts are found to be rich in ribonucleoproteins, there is no reason to suppose that their growth promoting activity is associated to any great extent with the ribonucleoprotein fraction.Of the non-embryonic material tested, the higher protein-split -products have shown greatest growth promoting power in stimulating nucleoprotein synthesis in growing cells. The products of partial breakdown of the nucleic acids have also shown activity.Both these types of material have been found in the products released by yeast cells injured by exposure to ultraviolet light. They may be released either as the result of increased cell permeability or as disintegratiori products of dead and dying cells, and are responsible, in part at least, for the proliferation- promoting properties of extracts of ire radiated yeast cells.Ribonucleic acids have been demonstrated in all mammalian tissues tested. Tn many tissues the amount of cytoplasmic ribonucleic acid is greater than the amount of nuclear desoxyribonucleic acid. When adult sheep tissues are compared with the corresponding embryonic tissues, the ratio of ribonucleic acid phosphorus to desoxyribonucleic acid phosphorus for any given tissue is in most cases, of the same order in the adult as in the embryo, although the total amount of nucleic acid in the embryonic tissue is higher than in the adult tissue.A ribonucleic acid has been isolated from liver and shown to be similar to yeast ribonucleic acid. It is present in the cytoplasm of the liver cell. The amount present in liver tissue under various conditions has been ascertained.Tumour tissues also contain ribonucleic acid. The total nucleic acid content of tumours is variable, but in most cases is of a high order.Rapidly growing tissues, embryonic or neoplastic, tend to be characterized by a high water content, a high total nucleic acid content, and a low acid soluble nucleotide content.