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Review Topic 1

Contents

Absorption of X rays

Direct and Indirect Action

Absorption of Neutrons

DNA Strand Breaks

Interactions of Radiation with Matter

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ABSORPTION OF X RAYS

The process by which x-ray photons are absorbed depends on:

the energy of the photons concerned and
the chemical composition of the absorbing material.

The Compton process dominates at high energies, characteristic of a cobalt-60 unit or a linear accelerator used for radiotherapy.

In the Compton process:

The photon interacts with what is usually referred to as a "free" electron, an electron whose binding energy is negligibly small compared with the photon energy.
Part of the energy of the photon is given to the electron as kinetic energy; the photon, with whatever energy remains, continues on its way, deflected from its original path.
In place of the incident photon there is a fast electron and a photon of reduced energy, which may go on to take part in further interactions.
The net result is the production of a large number of fast electrons, many of which can ionize other atoms of the absorber, break vital chemical bonds, and initiate the change of events that ultimately is expressed as biological damage.

Both the Compton process and photoelectric absorption occur for photon energies characteristic of diagnostic radiology, the former dominating at the higher end of the energy range (such as fluoroscopy) and the latter being most important at lower energies (such as mammography).

Figure 1

The percentage of photon dose attributable to a given process as a function of photon energy is shown.

In the process of photoelectric absorption:

The x-ray photon interacts with a bound electron in, for example, the K, L, or M shell of an atom of the absorbing material.
The photon gives up all of its energy to the electron; some is used to overcome the binding energy of the electron and release it from its orbit, while the remainder is given to the electron as kinetic energy of motion.

DIRECT AND INDIRECT ACTION OF RADIATION

The biological effects of radiation result principally from damage to DNA, which is the critical target. When any form of radiation -- x- or g-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, thus initiating the chain of events that leads to a biological change. This is the so-called direct action of radiation; 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 that 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 orbital electron in the outer shell. This state is associated with a high degree of chemical reactivity.)

Figure 2

In direct action a secondary electron resulting from absorption of an x-ray photon interacts with the DNA to produce an effect. In indirect action the secondary electron interacts with, for example, a water molecule to produce a hydroxyl radical, which in turn produces the damage to the DNA. The structure of DNA is shown schematically.

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.

Charged particles (e.g., alpha particles and electrons) are directly ionizing; that is, provided the individual particles have sufficient kinetic energy, they can directly disrupt the atomic structure of the absorber through which they pass and produce chemical and biological changes. Electromagnetic radiations (x- and g-rays) and neutrons are indirectly ionizing. They do not produce chemical and biological damage themselves, but when they are absorbed in the material through which they pass they give up their energy to produce fast-moving charged particles.

Example of Indirect Action:

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 rays, the water molecule may become ionized producing H₂O^⁺, which is an ion radical. (An ion is an atom or molecule that is electrically charged because it has lost an electron.)
In the case of water, the ion radical reacts with another water molecule to form the highly reactive hydroxyl radical (OH·). The hydroxyl radical possesses nine electrons, so one of them is unpaired.
OH· is a highly reactive free radical and can diffuse a short distance to reach a critical target in a cell. For example, it is thought that free radicals can diffuse to DNA from within a cylinder with a diameter about twice that of the DNA double helix.

It is estimated that about two thirds of the x-ray damage to DNA in mammalian cells is due to the hydroxyl radical. Indirect action is illustrated in the figure above. This component of radiation damage can be modified by chemical means -- by either protectors or sensitizers, as opposed to the direct action which cannot be modified.

ABSORPTION OF NEUTRONS

Neutrons are uncharged particles. For this reason they are highly penetrating compared with charged particles of the same mass and energy. They are indirectly ionizing and are absorbed by elastic or inelastic scattering.

Fast neutrons differ basically from x rays in the mode of their interaction with tissue. X-ray photons interact with the orbital electrons of atoms of the absorbing material by the Compton or photoelectric process and set in motion fast electrons. Neutrons, on the other hand, interact with the nuclei of atoms of the absorbing material and set in motion fast recoil protons, alpha particles, and heavier nuclear fragments.

In soft tissues, the interaction between incident neutrons and hydrogen nuclei -- which are, of course, single protons -- is the dominant process of energy transfer.

At energies above about 6 MeV, non-elastic scattering begins to take place and assumes increasing importance as the neutron energy rises.

The neutron may interact with a carbon nucleus to produce three alpha particles or with an oxygen nucleus to produce four alpha particles. These are the so-called spallation products, which become very important at higher energies.

DNA STRAND BREAKS

Deoxyribonucleic acid (DNA) is a large molecule which has the well-known double helix structure. It consists of two strands, held together by hydrogen bonds between the bases. The backbone of each strand consists of alternating sugar - phosphate groups. The sugar involved is deoxyribose. Attached to this backbone are four bases, the sequence of which specifies the genetic code. The bases on opposite strands must be complementary; adenine pairs with thymine, while guanine pairs with cytosine. This is illustrated in the simplified model of DNA in strand A of the figure below.

Figure 3

A: Two- dimensional representation of the normal DNA helix. Note the complementary base pairs described above.
B: A break in one strand is of little significance because it is repaired readily, using the opposite strand as a template.
C: Breaks in both strands, if well separated, are repaired as independent breaks.
D: If breaks occur in both strands and are directly opposite or separated by only a few base pairs, this may lead to a double-strand break in which the chromatin snaps in two pieces.

When cells are irradiated with x rays, many breaks of a single strand occur. These can be observed and scored as a function of dose if the DNA is denatured and the supporting structure stripped away. In intact DNA, however, single-strand breaks (SSBs) are of little biological consequence as far as a cell killing is concerned because they are readily repaired using the opposite strand as a template (see above figure, strand B). If the repair is incorrect (misrepair), it may result in a mutation. If both strands of the DNA are broken, and the breaks are well separated (see above figure, strand C), repair again occurs readily since the two breaks are handled separately.

By contrast, if the breaks in the two strands are opposite one another, or separated by only a few base pairs (see above figure, strand D), this may lead to a double-strand break (DSB). That is, the piece of chromatin snaps into two pieces. A double-strand break is believed to be the most important lesion produced in chromosomes by radiation; as is described in the next topic, the interaction of two double-strand breaks may result in cell killing, mutation, or carcinogenesis.

Try this link for more on the science of ionizing radiation.

FURTHER READING

Goodwin PN, Quimby EH, Morgan RH: Physical Foundations of Radiology. New York, Harper & Row, 1970.

Hall EJ: Radiobiology for the Radiologist, 5th Ed. Philadelphia, Lippincott Williams & Wilkins, 2000.

Johns HE, Cunningham JR: The Physics of Radiology, 4th Ed. Springfield, IL, Charles C Thomas, 1983.

Mettler FA, Upton AC. Medical effects of ionizing radiation, 2^ndEd. Philadelphia, W.B. Saunders Company, 1995.

Rossi HH: Neutron and heavy particle dosimetry. In Reed GW (ed): Radiation Dosimetry: Proceedings of the International School of Physics, pp 98-107. New York, Academic Press, 1964.

Smith VP (ed): Radiation Particle Therapy Philadelphia, American College of Radiology, 1976