The Fluid-Flow Theory and Indirect Action of Radiation

Abstract

In 1937, Dr. Failla published a “fluid-flow” theory of the biologic action of ionizing radiation (1), postulating that ionization increased the osmotic pressure within the cell, causing it to swell. This stress, together with the production of deleterious substances and local damage to membranes, would serve to account for cell death under certain conditions and for cell recovery under others. Failla and Sugiura (2), in 1939, reported findings in irradiated mouse sarcoma 180 tumor cells which tended to support this theory. They tested the postulate further by injecting tumors with distilled water following local treatment with roentgen rays (3) and found greater destruction in these tumors than in those injected with saline. In the ensuing years, the attention of radiobiologists became focused on the nucleus, on cell division, and on chromosome aberrations. This was due, in part, to the resurgent interest in the target theory and the RBE studies demonstrating the importance of specific ionization. Many of the cellular findings appeared to be satisfied by target theory mechanisms. Some of these observations may be mentioned, i.e., dose effect curves based on killing of micro-organisms and on mutation frequency, localized irradiation of chromosomes, lack of effect of temperature and metabolic rate in modifying many radiation effects, lack of effect of protraction or fractionation in altering certain radiation injuries, and the finding of optimal specific ionization for efficiency of radiation production of chromosome aberrations. Interest in chemical aspects was, however, kept alive by Dale's work on enzymes (4), Friedewald and Anderson's studies on rabbit papilloma virus (5), and investigations of radiation inactivation of bacteriophage by Luria and Exner (6). In 1941, a group of us including Dr. Failla carried out a number of experiments in an attempt to explain the finding that sea urchin sperm irradiated in concentrated suspension were relatively radioresistant, but when irradiated in dilute suspension in sea water were very radiosensitive, in respect to viability (7). The results of these experiments enabled us to differentiate between effects produced directly on the cell, nucleus, etc., and those resulting from an indirect action through the medium (8). Our interpretation of the mechanisms was based on the earlier works of Risse (9) and of Fricke (10). We used Fricke's terminology in postulating that x-radiation produced “activated water molecules” in the medium. This finite quantity of activated molecules with a relatively short life could either be dissipated upon the experimental units in the medium or upon other molecules present.