The Biological Effect of Radium

Abstract

MICROSCOPICAL sections taken at intervals from irradiated growths in process of resolution show a definite sequence of changes for both radium and X-rays (1, 2, 3). These consist of, first, a latent period during which no changes are observed in the tumor cells. At this time, however, an inflammatory reaction is taking place in the stroma. There is hyperemia and exudation of polys and lymphocytes. Following this period alterations appear in the malignant cells: they swell to giant proportions. The third phase is represented by keratinization. This is followed by disintegration and, finally, deposition of fibrous tissue. The lymphocytes, fibroblasts and dilated capillaries dominate in this late picture. We observe, then, an orderly sequence of changes spread over a considerable length of time but in no way comparable to caustic or thermal effects. In review, we see mesoblastic activity on the scene first and last. The second phase of the reaction wherein we see the swelling of the malignant cells has given rise to the thought that irradiation generates new electrolytes in the malignant cell, which, in turn, alters osmotic relationships and draws in water (4). It is spoken of as the ultimate effect of irradiation and obviously the nature of the process involved assumes considerable importance. I have been unable to find any experimental foundation for conclusions in this regard and undertook some with egg white, realizing, of course, that this is not malignant tissue, but since it has a very high swelling rate any deviation consequent to irradiation ought to manifest itself. Using 5 c.c. of egg white I exposed it from 100 to 5,000 milligram-hours. Each specimen was then put in an egg membrane dialyzer, immersed in normal salt and the swelling measured against controls of the same lot of egg white, in the same container, both before and after. The second control, i.e., that one run after the irradiated specimen, usually has a higher rate than the first, because of a certain amount of autolysis taking place in the protein on standing. The results of these experiments reveal a shift in favor of the irradiated specimen only in the extreme high exposures, where molecular disintegration is taking place, as evidenced by the smell of hydrogen sulphid. Under 2,000 milligram-hours there is no shift, and our conclusions are that there is no reason to believe that a change in osmotic properties is accomplished by irradiation applied therapeutically. We join with Ewing (4) when he says,“The ultimate action of rays on cell structure has not been explained by physics or chemistry.” Murphy (5), of the Rockefeller Foundation, experienced negative results when investigating direct effects, and we are facing the fact that a particular susceptibility of tumor cells to direct irradiation has never been established. The explanation of a physiologic response has a much stronger position.