ERIC J. HALL M.A., D. Sc.,Professor of Radiology Columbia University, NYC

Radiobiology For The Radiologist, Second Edition 1978


   For diagnostic radiology, photons are used in the energy range where photoelectric absorption dominates over Compton. Z, the atomic number, is defined as the number of positive charges in the nucleus: it is therefore the number of protons in the nucleus. Because the mass absorption coefficient varies critically with Z, the x-rays are absorbed to a greater extent by bone because it contains elements, such as calcium, which have a high atomic number. This differential absorption in materials of high Z is one of the basic principles behind the familiar appearance of the radiograph. On the other hand, for radiotherapy high-energy photons in the megavoltage range are preferred, because in this case the Compton process is overwhelmingly important. As a consequence, the absorbed dose is approximately the same in soft tissue, muscle, and bone, such that the now unwanted differential absorption in bone, which poses a problem when lower-energy photons are used for therapy, is avoided. While the differences between the various absorption processes are of practical importance in radiology, the consequences from a radiobiological point of view are minimal. Whether the absorption process is the photoelectric or the Compton, most of the energy of the absorbed photon is converted into the kinetic energy of a fast electron.

FIG. 1-3. Illustrating the direct and indirect actions of radiation.

   The structure of DNA is shown schematically; the letters S, P, A, T, G, and C represent sugar, phosphorus, adenine, thymine, guanine, and cytosine, respectively.
   Direct action: A secondary electron resulting from absorption of an x-ray photon interacts with the DNA to produce an effect.
   Indirect action: The secondary electron interacts with, for example, a water molecule to produce an OH- radical, which in turn produces the damage to the DNA.

   It is estimated that free radicals produced within a cylinder of radius 20 A can affect the DNA. The indirect action is dominant for sparsely ionizing radiations such as x-rays.

   It is important to avoid confusion between directly and indirectly ionizing radiation, on the one hand, and the direct and indirect actions of radiation on the other. Despite the vast amount of research that has been carried out in radiobiology, there is still an element of doubt concerning the identity of the critical targets or vital structures in the mammalian cell which must be damaged in order to kill the cell. It is almost certain that the DNA in the chromosomes represents the most critical target, though it is also likely that the nuclear membrane is important too. For the purpose of this first chapter, the identity of the critical target is not important, so long as it is appreciated that there are discrete sites within the cell which must be damaged before the cell can be killed. When any form of radiation-x-rays, -y-rays, charged or uncharged particles-is absorbed in biological material, there is a possibility that it will interact directly with the critical targets in the cells. The atoms of the target itself may be ionized or excited, so initiating the chain of events that leads to a biological change. This is the so-called direct action of radiation, which is illustrated in Figure 1-3; it is the dominant process when radiations with high linear energy transfer (LET), such as neutrons or alpha particles, are considered.

  Alternatively, the radiation may interact with other atoms or molecules in the cell (particularly water) to produce free radicals which are able to diffuse far enough to reach and damage the critical targets. This is called the indirect action of radiation. A free radical is a free (not combined) atom or molecule carrying an unpaired or odd orbital electron. An orbital electron not only revolves around the nucleus of an atom but also spins around its own axis. The spin may be either clockwise or counterclockwise. In an atom or molecule with an even number of electrons, spins are paired; that is, for every electron spinning clockwise, there is another one spinning counterclockwise. This state of affairs is associated with a high degree of chemical stability, regardless of whether the atom or molecule is electrically neutral or charged (ionized). In an atom or molecule with an odd number of electrons there is one odd electron for which there is no other electron with an opposing spin; this is an unpaired electron. This situation is associated with a high degree of chemical reactivity, regardless of whether the atom or molecule is electrically charged or neutral.

   For simplicity we will consider what happens when radiation interacts with a water molecule, since 80% of a cell is composed of water. As a result of the interaction of a photon of x- or -y-rays, or a charged particle such as an electron or proton, the water molecule may become ionized. This may be described by the equation: H20 -> (H20+) + e- H2O+ is an "ion radical." An ion is an atom which is electrically charged because it has lost an electron. A free radical is a species which contains an unpaired electron in the outer shell, as a result of which it is highly reactive. (H2O+) is both charged and has an unpaired electron; consequently, it is both an ion and a free radical. Ion radicals have an extremely short lifetime, on the order of 10-10 sec. They decay to form free radicals, which are not charged, but which still have an unpaired electron. In the case of water, the ion radical reacts with another water molecule to form the highly reactive hydroxyl radical OH-: (H20+) + H20 -> (H3O+) + OH- The OH- possesses a total of nine electrons, and so one of them is unpaired. It is a highly reactive free radical and can diffuse a short distance to reach a critical target within a cell.

   For example, it is thought that free radicals can diffuse into DNA from within a cylinder having a diameter of approximately 20 A. It is estimated that 75% of the x-ray damage to DNA in mammalian cells is due to the OH- radical. This indirect action is illustrated in Figure 1-3. In practice, of course, the situation is very much more complex, even for water, and is vastly more complicated when the absorbing material consists of large biological materials. For the indirect action of x-rays the chain of events, from the absorption of the incident photon to the final observed biological change, may be described as follows:

      There are vast differences in the time scale involved in these various events. The ion radicals have a lifetime of about 10-11 sec, and the free radicals perhaps 10-5 sec, while the step between the breakage of chemical bonds and the expression of the biological effect may be days, months, or years, depending on the consequences involved.