radiation, ionizing

radiation, ionizing X-rays were discovered by Röntgen in Germany in November 1895. This caused tremendous public interest and very rapidly they started to be used for many medical diagnostic purposes. Within just a few years it was realized that high radiation doses from X-rays could cause severe skin burns, cancer in exposed tissues, and even death. This resulted in steps being taken to reduce exposures, although in the early years after their discovery it was assumed that only high radiation doses from X-rays could cause cancer. By the late 1920s it had become apparent, from the studies of Müller on the fruit fly, Drosophila, that radiation damage from X-rays could cause effects in future generations, and through to the 1950s this was the principle cause for concern at lower radiation doses. By the early 1950s, however, follow-up studies of the A-bomb survivors in Japan and other exposed populations were showing that radiation-induced leukaemia and other cancers could arise even at low levels of exposure. The principle long-term effect of exposure to low doses of ionizing radiation is now considered to be the induction of cancer.

Ionizing radiations include X-rays, neutrons, cosmic rays, and radiation from radioactive materials, such as alpha particles, beta particles, and gamma rays. When ionizing radiations pass through matter, energy is deposited in the material concerned. Alpha and beta particles, being electrically charged, deposit energy through electrical interactions with electrons in the material. Gamma rays and X-rays lose energy in a variety of ways, but each involves liberating atomic electrons, which then deposit energy through interactions with other electrons. Neutrons also lose energy in various ways, an important means being through collisions with hydrogen nuclei, which are single protons. The protons are set in motion and, being charged, they again deposit energy through electrical interactions. So in all cases, these radiations ultimately produce electrical interactions in the material and this can give rise to ionizations when a neutral atom or molecule becomes charged as a result of a loss of an electron. Once removed from an atom, an electron may in turn ionize other atoms or molecules. When ionizing radiation passes through cellular tissue, it produces charged water molecules. These break up into entities called free radicals, such as the free hydroxyl radical (OHl) composed of an oxygen atom and a hydrogen atom. These free radicals are highly reactive chemically and can themselves alter molecules in the cell. One molecule of particular importance in relation to radiation damage is deoxyribonucleic acid (DNA), found in the nucleus of the cell. Radiation may ionize a DNA molecule, leading directly to a chemical change, or the DNA may be changed indirectly when it interacts with a free radical produced in the water of the cell by radiation. In either case, the chemical change can cause a harmful biological effect, leading ultimately to the development of cancer or inherited genetic defects. The quantification of these effects has provided the basis for radiation protection standards.

The principal quantity used to assess exposure to radiation is the absorbed dose, with the unit of the gray, Gy (equivalent to a deposition of energy of 1 Joule/kg). The gray can be multiplied by a ‘weighting factor’ to take account of the effectiveness of different radiations in causing damage to tissues. Thus X-rays, gamma rays, and beta particles have a ‘radiation’ weighting factor of 1; for alpha particles it is 20. The unit of this weighted dose is the sievert, Sv, and it is termed the equivalent dose.

Exposure to ionizing radiation comes from a variety of sources. There are sources of natural origin, such as cosmic rays from the atmosphere, gamma rays from radioactive materials in the ground and in our own bodies, and inhalation of radon; we can be exposed as a result of medical diagnostic procedures and treatment; radiation is also present in the environment as a result of nuclear weapons testing and as a consequence of discharges from nuclear sites and from nuclear accidents. For most people the main source of radiation exposure is natural background, which, in the UK, gives a radiation dose of about 2.2 millisieverts (mSv) a year. There can be substantial differences between individuals, mainly reflecting differences in exposure to radon gas and its decay products.

Early radiation effects

The effects of ionizing radiation soon appear if a person receives a sufficient radiation dose. A very high radiation dose to the whole body can cause death within a matter of weeks. For example, an absorbed dose of 5 Gy (5000 mGy) or more received instantaneously by the whole body would probably be lethal unless treatment were given. Death would occur because of damage to the bone marrow and the gastrointestinal tract, both of which have rapidly-dividing and hence sensitive cell populations. If the same dose were instead restricted to a limited part of the body, it might not prove fatal but early effects could still occur. Thus an instantaneous absorbed dose of 5 Gy or more to the skin would probably cause erythema within a week or so. Higher doses would lead to more serious damage and breakdown of the skin structure. Similar doses to the testes or ovaries might cause sterility. However, if the same radiation dose were to be received over a period of weeks or months, there would be the opportunity for body cells to repair some damage, with much less early sign of injury. Even in the absence of early signs, however, tissues could still have been damaged, with the effects becoming manifest only later in life, or perhaps in the irradiated person's descendants. The most important of these late effects is cancer, which is always serious and frequently fatal.

Radiation-induced cancer

Although the cause of most cancers remains unknown or poorly understood, exposures to a wide range of agents, such as tobacco smoke, asbestos, ultraviolet radiation, chemicals, and ionizing radiations, are all known to induce them. The development of cancer is a complex cellular process that occurs in several stages, usually taking many years. Radiation appears to act principally at the initiation stage by causing mutations in the DNA of normal cells in tissues. It is usually considered that damage is caused by double-strand breaks (DSBs) in DNA, which are not readily repaired. The production of DSBs can result in a cell entering a pathway of abnormal growth that can sometimes lead to development of a malignancy. In recent years, much has been learned about the processes by which radiation exposure leads to DNA damage, and also about the cellular systems that act to repair, or misrepair, such damage and the way mutations can arise. This information provides supporting evidence for the long-standing belief that, although the risk of cancer after low doses of radiation may be very small, there is no dose, no matter how low, at which we can completely discount the risk. For radiation protection purposes it is therefore assumed that the risk of cancer increases progressively with the dose, with no threshold.

Advances in knowledge also indicate that a person's genetic constitution influences the risk of cancer after irradiation. At present we can identify only rare families who may carry increased risk. In future, techniques may become available that allow the identification of more groups of individuals with increased sensitivity to irradiation. This is an important factor in medical exposures, as individuals treated medically — for example by radiotherapy — might have quite different responses to radiation exposure.

It is also known that tissues vary in their response to radiation-induced cancer, thus the lung and the gastrointestinal tract are particularly sensitive, whereas the brain and muscles are very insensitive. In assessing the risks of exposure to radiation we therefore have to allow for these differences in sensitivity.

How can we calculate the risk of cancer from exposure to radiation? Suppose we know the number of people in an irradiated group and the doses they have received. By observing the incidence of cancer in the group and analyzing it in relation to the size of the radiation dose and the number of cases expected, in another similar but unirradiated group, we can estimate the raised risk of cancer per unit radiation dose. This is commonly called a risk factor. It is most important to include data for large groups of people in these calculations so as to minimize the statistical uncertainties in the estimates and to take account of factors such as age and gender that can effect the spontaneous development of the disease. For this reason, the main source of information on risks of radiation-induced cancer comes from studies on nearly 100 000 survivors of the atomic bombs dropped at Hiroshima and Nagasaki in 1945. Other risk estimates for the exposure of various tissues and organs to X-rays and gamma rays can be obtained from studies of people exposed to external radiation for the treatment of non-malignant or malignant conditions or for diagnostic purposes, and also from people in the Marshall islands in the Pacific who were exposed to severe fallout from atmospheric nuclear weapons testing. Information on the effects of internally incorporated alpha-emitting radionuclides comes from miners exposed to radon and its decay products, from workers exposed to radium in luminous paint, from patients treated with radium for bone disease, and from other patients given an X-ray contrast medium containing thorium oxide, which tended to concentrate in the liver. Long-term follow-up studies on these groups of people have allowed both national and international bodies, such as the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and the International Commission on Radiological Protection (ICRP), to estimate risks of radiation-induced cancer in various tissues as a function of time and age after exposure. A striking observation from these studies has been that whilst radiation-induced leukaemia starts to occur within a few years, and most have occurred by about thirty years following radiation exposure, in the case of most solid cancers the so-called latent period, before any induced cancers appear, may be five, ten, or even twenty years. Subsequently cancers may then occur over the remaining lifespan of the individual. For this reason, exposed groups must be followed for very many years to obtain accurate estimates of the total risk of cancer. In practice, as no populations have yet been followed for their entire lifespan, it is necessary to predict how many excess cancers will have been found by the time all the survivors have died. Various mathematical methods are used for this purpose, which inevitably introduces some uncertainty in the risk estimates.

Not all cancers are fatal. Mortality from radiation-induced thyroid cancer is about 10%, from breast cancer about 50%, and from skin cancer only about 1%. Overall, the risk of inducing any cancer by uniform irradiation of the whole body is about half as great again as the risk of inducing a fatal cancer. In radiological protection, the risk of fatal cancer is naturally of most concern. Present estimates of the risk of radiation-induced fatal cancer provided by ICRP are 1 in 20 per Sv for exposure of a population of all ages and 1 in 25 per Sv for a working population. These values apply to a mixed population of all ages; there will be differences in sensitivity in males and females as well as between individuals of different ages.

Radiation-induced hereditary disease

Apart from cancer, the other main late effect of radiation is hereditary disease. As with cancer, the probability of hereditary disease, but not its severity, depends on the dose. Genetic damage arises from irradiation of the testes and ovaries, which produce sperm cells in males and the egg cells in females. Ionizing radiation can induce mutations in these cells or in the stem cells that form them. Mutations occur as a result of structural changes to the DNA in single germ cells, which subsequently carry the hereditary information in the DNA through to future generations. The hereditary diseases that may be caused vary in severity from early death and serious mental defects to relatively trivial diseases such as skeletal abnormalities and minor metabolic disorders.

ICRP has assessed the risk of severe hereditary disease in a general population of all ages exposed to low doses and dose rates. It estimated a risk factor of 1 in 100 per Sv for such diseases appearing at any time in all future generations. Mutations leading to diseases that are strictly heritable, such as haemophilia, make up about half of the total, with the remainder mainly coming from a group of so-called multifactorial diseases, such as diabetes and asthma. Estimating the risk of multifactorial diseases is complex, as there is interplay of the genetic and environmental factors that influence the development of these disorders.

In genetic terms, irradiation of the testes and ovaries is potentially harmful only if it occurs before or during the reproductive period of life. For people who will not subsequently have children, there is, of course, no hereditary risk. Since the proportion of a working population that is likely to reproduce is lower than that in the general population, the risk factor for workers is smaller. ICRP estimates 1 in 170 per Sv for hereditary disease in all future generations.

Summary and conclusions

At high radiation doses, significant effects can occur in exposed individuals within a short time of exposure, and in severe cases this can lead to early death. At low radiation doses, the principal concern is the risk of radiation-induced cancer in exposed individuals and hereditary disease in their descendants. The risks of these late effects have been quantified and this provides the basis for recommendations on limits for exposure.

John W. Stather

See also cancer; free radicals; radioactivity; X-rays.