702 RADIATION PROTECTION are realized. The concept of RBE originated in the radiobiological literature (1-3), and in a strict sense it is applicable only under rather stringent experimental conditions. These conditions include uniform distribution of dose throughout the biological object, and an accurate knowledge of the ab sorbed dose delivered. The term has been used widely, however, under circm. stances in which the absorbed dose is only poorly known or not known at all, and where the distribution of dose is unknown or markedly non → homogeneous. This has been responsible in part for the degree of disrepute into which the term has fallen. Actually, there is a need for three tems to span the meanings ascribed to "RBE". One is required for use in the strict radiobiologi cal context originally meant for the tem. A second is required to cover those situations in which dose in the biological material is not, or is only poorly known, and in which dose distribution may be poorly known or unknown. A term to compare effectiveness of radiations under these conditions is re quired practically. And of course, + it is necessary to ascribe RBB values for practical, daily use in Health Physics under conditions far from radiobiologi cally strict, and it is necessary to have a term for these "legislated RBB's". These considerations are being deliberated by committees of the ICRP and NCRP, and no terms will be designated here. Theoretical Importance of RBE The fact that RBB exists has considerable significance with regard to fundamental interactions of ionizing radiation, with tissue, and a great deal of study and thought has been devoted to the problem. There is as yet no generally accepted theory to account for the primary actions of radiation that 1 RADIATION PROTECTION 703 lead to the effects or manifestations that are observed. The use of radia tions with different RBE values (different LET, discussed below) represents a most powerful tool for investigation in this area, particularly when com bined with changes in the imediate environment of the biological material (1-4). It must be recognized that energy from ionizing radiation is deposited in discrete events within tissue, and that absorbed dose in rads entails a macroscopic concept and always involves, to some degree, an averaging of energy deposited in discrete units. It is generally believed that the fact of RBE derives from differences in the manner in which radiation energy is deposited at a sub microscopic level, although the precise mechanisms in Theoretically and from studies with volved are far from being understood. gases it is well known that the lower the velocity and the greater the charge of an ionized particle*, the more densely packed are the ionizing events pro duced, or the more energy is dissipated per unit length of track. The density of ionization has been described in tems of specific ionization, rate of energy loss (REL) or linear energy transfer (LET), with LET in most favored use in biology and medicine. It might be expected that if only one, or a given number of ionizing events within a given biological volume is required to produce a given bio logical effect, then the RBB would increase with increasing LBT, as the proba bility of the required mumber of events occurring in a given volume increases. *Electromagnetic rays produce the bulk of their ionization by means of secondary ionizing electrons resulting from electron shell interactions. Neutrons produce all of their ionization by means of nuclear interactions, with resultant charged particles. 704 RADIATION PROTECTION As will be indicated below, this has been found to be true in many bio – logical systems studied. With further increasing LET, if only a given number of ionizing events per unit volume is required, a point of saturation would be expected to be reached beyond which some of the events would be "wasted", and the RBE LET. curve would again begin to decline. This also has been observed in some systems, and is in accord with target theory (2). If RBB vs energy is considered, however, an additional factor must Even if the RBE vs LET curve should increase in. be taken into consideration. definitely, the RBE vs energy curve still should go through a maximum for any one type of radiation (5). This stems from the fact that the LET energy curve must go through a maximum because at lower energies, or near the end of the "Bragg curve" for a single particle, the effective charge of the par ticle becomes less and thus the rate of ionization is decreased. The maxi mum LET along the track of a single energetic proton is 93 kev/micron, and occurs when the energy has decreased to 80 kev. Thus a maximum appearing at low energies in an energy - RBB curve does not usually indicate a saturation effect. The approximate energy at which a peak in a neutron energy curve might be expected has been calculated to be approximately 400 kev (6). Recently, in the course of experimental determination of LET using RBE a spherical ionization chamber containing tissue equivalent gas at various pressures (6), it became evident that LET as an expression of the distribu tion of energy deposition on a micro scale has serious limitations. The LET spectrum was found to vary with the size of the small volume of tissue being considered. In addition, the LET concept does not take into account ade quately the behavior of secondary or delta rays. Rossi (5,6) has introduced RADIATION PROTECTION 705 a new approach to correct to a degree the deficiencies of the LET concept. This involves a measurement and consideration of the dose distribution in "y", defined as the size of an event within a small sphere of tissue (passage of one ionizing particle) divided by the sphere diameter. Y is expressed in kev/micron, as is LET, These measurements provide an approach for studying further the possible "target" size in biological specimens. It remains to be seen to what degree this approach will shed additional light on the problem of RBE. Determination of RBB A variety of organisms and experimental conditions have been used in RBE studies. It is desirable that biological criteria of effect or "endpoints" that can be quantified be employed, and accurate dose measurements are of paramount importance. Data on low LET radiations is provided adequately by use of the "standard" X - or gamma radiations. For high LET studies, the most accurate technique involves the "single track segment" approach (1, 3, 4) in which microorganisms are exposed at various points along the "Bragg curve" of primary charged particles and thus can be exposed in narrowly defined intervals of LET. Either alpha emitting isotopes, or protons, tritium, alpha particles or heavier stripped muclei accelerated in a cyclotron or similar machine can be used. Dosimetry under these conditions is frequently difficult, and the technique in general is limited to very small specimens, such as microorganisms, or cell cultures because of the poor penetrability of the densely ionizing particles. For high LET work with intact mammals, it is necessary to use uncharged particles, neutrons, to obtain adequate penetration. Fast neutrons have been generally used for this purpose, and a wide variation of energy of the recoil protons, and thus of LET can be obtained. Thermal 706 RADIATION PROTECTION neutrons alone produce a 0.6 Mev recoil proton from collisions with nitro gen atoms; however the inability to vary the energy of the heavy particles and the accompanying gamma radiation from interaction with the hydrogen in tissue produced a "mixed” radiation unsuitable for the general RBB studies. If either compounds are injected into mice just prior to exposure Li6 B10 ог в to thermal neutrons, a very high percentage of the dose delivered is due to 3 recoil H3, He4, ΟΣ Li7 particles of high LET (8, 9). Fast neutrons are produced easily over a wide energy range; however with most sources a very wide smear of fast neutron energies is produced. Even with a monoenergetic neutron beam, the neutrons are scattered within tissue. Recoil protons of varying energies are produced. Thus a "smear" of LET values results. The entire LET spectrum can be presented, or a mean Obtaining a true average involves the formidable value can be calculated. task of integrating over all possible distributions, including the change in LBT over the path length of each ionizing particle. By taking advantage of the penetrability of fast neutrons, it has been possible to obtain "RBB" values* in small, and large animals as well. These studies have included a variety of biological criteria, to be indicated below. It has not been possible as yet to obtain experimental RBB values for some of the very high energy charged particles encountered in cosmic radiation. *In all studies other than with microorganisms, the question of to what degree the experimental conditions meet the exacting requirements for an RBB determination in the strict radiobiological sense must be considered. |