Chapter 10 Radiation and Health. Large Doses It was noted earlier that radiation can produce biological effects. Around the turn of the century a number of experiments were carried out, which, would be characterized today as dangerous and foolhardy. It was found that ionizing radiation was capable of developing skin burns and could cause hair to fall out. In 1899, Stenbeck and Sjögren from Sweden used radiation to remove a tumor from the nose of a patient. This showed that radiation in large doses could be used to kill cancer cells. In the early years, when radium was used for treatment, the sources were made in the form of capsules or small tubes. The procedure for radium treatment was either to use a large source of radium (teletherapy) or to use a number of small sources for brachytherapy. In the latter case, paraffin wax was often used and formed to suit the part of the body to be irradiated. Small needles of radium were then sealed into the wax. This procedure gave a good dose distribution when skin ailments and tumors were treated. The general view at that time was that the radiation from radioactive sources was healthy and was a good treatment for most sufferings. Figure 10.1 (next page) shows an advertisement from 1913. Some people made good money by producing radioactive drinking water. A number of small towns in middle Europe such as Badgastein, Baden-Baden, Marienbad, and Karlovy Vary had radioactivity in their water and were con- sidered to be healthy places. With the use of a jar and some radium salt (Figure 10.1), the water was saturated with radon when radium disintegrated. The belief was that by drinking this water you received “curative” radioactivity. In those days, like today, some © 2003 Taylor & Francis 116 Radiation and Health Figure 10.1. An advertisement from 1913 for radioactive drinking water. A jar with water, a cylinder and some radium salt was used. When Ra-226 disintegrates, radon is formed and is released into the water. When the tap was opened, radon was found in the water. The radiation doses were small and the whole system was rather harmless. (Reproduced with permission from R.F. Mould (1980).) © 2003 Taylor & Francis 117 Large Doses people voluntarily tried out methods that had not been tested or proved effective. In the early years, people were careless in the use of radiation and the handling of radioactive sources. The reason for this negligence was a lack of knowledge about radiation and its biological effects. Today, there is great deal of information about the effects of ionizing radiation, a great contrast to the lack of knowledge about the many chemicals in use. However, researchers in the radiation field have not been able to transmit this information to the public. The result is that the public has only an incomplete knowledge about radiation and radiation health effects. In spite of the fact that other human activities are far more hazardous than radiation, many people are unnecessarily afraid. Because large doses of radiation are known to kill cells, there is the possibilty of using radiation to treat cancer when localized to a small area of the body. Similar large whole-body doses can lead to death, which occurs in the course of days or weeks. When considering medium and small doses, the biological effect is considerably more difficult to predict. The reason for this is the time lag between the exposure and the observable biological effect. For solid cancers it may be several decades. Marie Curie, and a number of the other radiation pioneers died from cancer; thus, there are reasons to believe that their work with radiation was involved. On the other hand, recent experiments have claimed that small doses may even have a positive health effect (see Chapters 11 and 12). In all discussions on the biological effects of radiation, the radiation dose is a key issue. Without knowledge about the size of the dose it is meaningless to discuss the effects. The relationship between the dose and effect is also a hot issue in the community of research scientists. Knowledge about the dose–effect curve is a requirement when discussing mechanisms and health risks of radiation. Dose–Effect Curves The effect of radiation depends upon the dose. The larger the dose, the larger the effect. This relationship is called the dose–effect curve and may be demon- strated with a simple example. When using an ordinary camera, you know that it is important that the film be exposed to the right amount of light. When exposed to a lot of light, the film becomes black, and when exposed to very little light,the film is hardly darkened . © 2003 Taylor & Francis 118 Radiation and Health The blackening of the film depends on the amount of light (i.e. the dose).This is illustrated in Figure 10.2. The S-shaped curve obtained is called the dose–effect curve. Figure 10.2. Dose–effect curve for the darkening of film. The horizontal axis represents the amount of light (dose) and the vertical axis gives the darkening (effect). In work with radiation and biological effects, the results are often given by such dose–effect curves. In radiobiology a lot of interest is concentrated on the form of dose–effect curves and, in particular, the form of the curves at small doses. Small doses will be discussed in the next chapter; here the discussion will deal with the effect of large doses. What is a Large Dose? In a discussion about the biological or health effects of radiation, the equivalent dose unit, the sievert, is often used. Again, the equivalent dose (Sv) is equal to the physical dose (Gy) multiplied by a radiation weighting factor (w R ). In the case of x- and γ-rays the weighting factor is 1. The dose in gray and the equivalent dose in sievert have the same value. However, in the case of radon and its daughter products which emit α-particles, a radiation weighting factor of 20 is used. Neutrons and other high energy particles have weighting factors larger than 1. Dose (amount of light) Effect (blackening of film) The amount of light which yields the best © 2003 Taylor & Francis 119 Large Doses The large dose region can be characterized in the following way: Annual doses of 2 mGy to 5 mGy (such as those attained from natural background radiation) are considered to be very small. The Use of Large Doses Large radiation doses are used for: • Sterilization of medical equipment Co-60 and Cs-137 γ-radiation are used to sterilize medical equipment. The doses delivered are on the order of 20 to 40 kGy. The purpose of the radiation is to kill bacteria, viruses, and fungi that contaminate equipment. • Radiation of food products The purpose is almost the same as for sterilizing equipment. The doses are, however, smaller, on the order of 5 to 10 kGy. Larger doses may change the taste of certain foods. • Radiation therapy In the radiation treatment of cancer, the purpose is to kill the cancer cells while allowing nearby healthy cells to survive. Much effort is carried out to achieve treatment protocols that will give the most effective treatments. The total dose given to a tumor is 10 to 80 Gy. A treatment protocol may include daily doses of 2 Gy, given 5 days per week. The type of radiation is usually in the form of high energy x-rays from linear accelerators (energies up to 30 MeV) which yield suitable depth dose curves (see Figure 6.3). It is also possible to use electron irradiation but the dosimetry becomes more complicated. The treatment is more effective when the radiation dose is split up into a number of smaller doses rather than giving the same total dose all at once. A dose of more than 1 to 2 Gy is considered to be large and a dose smaller than 0.1 to 0.2 Gy (100 to 200 mGy) is considered to be small. © 2003 Taylor & Francis 120 Radiation and Health The “fractioned dose treatment protocol” has the advantage of partly solving the problems with hypoxic cells in a tumor (see Chapter 12). Experience has shown that fractionated dose treatment yields the best results for tumor destruction while minimizing damage to healthy tissue. • Bone marrow transplantation In combination with bone marrow transplantation which is used for the treat- ment of certain illnesses, whole-body radiation is sometimes used with chemotherapy to deplete the original bone marrow. The dose used is about 12 Gy (6 days with a daily dose of 2 Gy). This dose is sufficient to completely destroy the bone marrow and would kill the patient if it were not for the immediate transplant of new compatible bone marrow. A number of people have been treated in this way. LD 50 Dose By definition, an LD 50 dose (abbreviation for “Lethal Dose to 50 percent”) is the dose that could kill 50 percent of the individuals exposed within 30 days. To arrive at a determination of the LD 50 dose, experiments like the following must be carried out. In typical experiments, rats, about 15 animals in each group, were given different whole-body doses. The number of animals dying in the course of 30 days was ob- served for each group. The result is given in Figure 10.3. The dose is given along the horizontal axis and the number of animals dying ( in percent for each group) is given along the vertical axis. The results show that no animals survived a dose of 10 Gy, whereas all rats survived a dose of 5 Gy. It can be seen that the LD 50 dose is approximately 7.5 Gy. © 2003 Taylor & Francis 121 Large Doses Figure 10.3. Dose–effect curve for radiation-induced death in rats. When humans and animals are irradiated, the blood-forming organs (in the bone marrow) will be the first to react. For doses of the order 1 to 2 Gy the number of white and red blood cells will decrease as shown in Figure 10.4. As a result of this, the immune system will fail and, after one to two weeks, life threatening infections may occur. If the radiation doses are smaller than 4 to 5 Gy, there is a good chance the bone marrow will recover and resume the production of blood cells. This takes place after 3 to 4 weeks and, consequently, 30 days is a reasonably chosen limit for the name acute radiation death. The LD 50 doses for a number of animals have been determined and some values are given in Table 10.1. Sin- gle cell organisms (for example bacteria, paramecium, etc.) may survive doses of the order 2,000 to 3,000 Gy. (This is taken into consideration in radiation treatment of food). In the case of humans there is not enough information to determine a precise LD 50 dose. The only information available has come from radiation accidents and the lethality depends not only on the dose and dose rate but also the post- exposure treatment given to the victims. Radiation dose (given in Gy) Effect (death of rats in percent) Adapted from A.P. Casarett (1968) with permission from A.P. Casarett © 2003 Taylor & Francis 122 Radiation and Health Table 10.1: LD 50 doses Figure 10.4. Whole-body irradiation results in changes in the number of blood cells. This figure shows the results of a moderate dose to rats. laminafoepyTyGniesoD goD5.3 yeknoM6 taR5.7 gorF7 tibbaR8 esiotroT51 hsifdloG32 namuH5-3 Time in days after radiation Percent of control Erythrocytes Platelets Granulocytes Lymphocytes Adapted from A.P. Casarett (1968) with permission from A.P. Casarett © 2003 Taylor & Francis 123 Large Doses Acute Radiation Sickness In 1906, Bergonie and Tribondeau found that there were different radiation sensitivities for different types of mammalian cells. Cells which grow rapidly (high mitotic rate), as well as undifferentiated cells, are the most sensitive. This implies that bone marrow, testes, ovaries and epithelial tissue are more sensitive than liver, kidney, muscles, brain and bone. Knowledge about this is of great importance for those exposed to ionizing radiation. The bone marrow and the epithelial cells of the intestine and the stomach as well as the gonads, the lymphocytes and skin develop the greatest damage. Damage to the bone marrow is the cause of death for whole-body doses in the region 3 to 10 Gy, whereas damage to the epithelial cells of the stomach and intestine is the cause of death for doses in the range from 10 to 100 Gy. For large doses, above100 Gy, damage to the central nervous system causes death. Figure 10.5. Survival curves for bone marrow cells of the mouse after irradiation with Co-60 γ-radiation. Adapted from A.P. Casarett (1968) with permission from A.P. Casarett Radiation dose (in Gy) Survival (in percent) © 2003 Taylor & Francis 124 Radiation and Health • Hematopoietic syndrome As mentioned above, the failure of the bone marrow is the cause of death for whole- body doses in the range of 3 to 10 Gy. The radiation may either kill these cells or arrest their development. A dose of 5 Gy will kill about 99% of the hematopoietic stem cells in mice (see Figure 10.5). These stem cells are neces- sary for the production of circulating blood cells (erythrocytes, granulocytes and platelets). A reduction of these cells will result in anemia, bleeding and infec- tions. The first sign of such radiation sickness is nausea, vomiting and diarrhea. This situation may disappear after a couple of days. Then, the consequences of lost blood cells become evident. Again, significant diarrhea may take place, often bloody, and a fluid imbalance may occur. This, together with bleeding, occurs in all organs. In addition, if infections occur, death may take place in the course of a few weeks. • Gastrointestinal syndrome For whole body doses of 10 to 100 Gy, the survival time is rarely more than one week. Damage to the epithelium of the intestine results in significant infections from the bacteria in the intestine itself. The production of blood cells is almost completely stopped, and those remaining in the blood disappear in the course of a few days. After 2 to 3 days almost all granulocytes will have disappeared from the circulation. The symptoms are pain in the stomach and intestine, nausea, vomiting and increasing diarrhea. A considerable loss of liquids and electrolytes will change the blood serum composition. There is an increased chance of infections. • Central nervous system syndrome For radiation doses above 100 Gy, the majority may die within 48 hours as the result of the central nervous system syndrome. The symptoms are irritability and hyperactive responses (almost like epileptic attacks) which are followed rapidly by fatigue, vomiting and diarrhea. The ability to coordinate motion is lost and shivering occurs followed by coma. Then respiratory problems occur which eventually lead to death. The symptoms described are due to damage to the brain, nerve cells and blood vessels. Immediately, permeability changes take place in the blood vessels re- sulting in changes in the electrolyte balance. The loss of liquid from the blood © 2003 Taylor & Francis [...]... been exposed to a whole-body dose of approximately 22.5 Gy The bone marrow dose was 21 Gy, whereas the dose to the brain was calculated to be 14 Gy 126 Radiation and Health Dose determination and radiation accidents Effect (number of radicals) It is a great challenge to determine the doses in radiation accidents The reason is obvious because accidents take place without warning and mainly without adequate... been exposed to radiation The man had acute radiation syndrome with damage to the blood forming tissue His blood counts went down almost like that shown in Figure 10. 4 He was treated © 2003 Taylor & Francis Corridor with antibiotics and several blood transfusions but died 13 days after the accident It is important to the know the dose he received Using electron spin resonance (ESR)-dosimetry the dose... animals die without visible damage to the brain A radiation accident In September 1982 a fatal radiation accident occured in a laboratory for radiationinduced sterilization of medical equipment in Norway An employee was exposed to a large γ-dose He was the only person at work when the accident happened A coincidence of technical failures with a safety lock and an alarm light, together with neglect of the... the safety routines, resulted in the fact that he entered the room with the source in the exposure position The drawing below shows the radiation facility The source is Co-60 with an activity of 2430 TBq Control room Concrete 1.25 m Control panel Co-60 source 2430 TBq Irradiation room Dosemeters Steel door The employee was found outside the laboratory in the early morning with clear signs of illness Since... determination Radiation workers usually have a dosimeter and, in the accident described above, the employees used film dosimeters The film can be used for doses up to about 1 Gy but is not applicable for fatal or near fatal doses Below, we demonstrate how the radiation dose was determined for this accident Radical formation in nitroglycerol tablets Irradiated during accident Calibration curve Radiation. .. were irradiated during the accident and rather stable radicals were formed The number of radicals formed yields information about the radiation dose Radical concentrations were measured using ESR spectroscopy (see Chapter 12 ) © 2003 Taylor & Francis E Sagstuen, H Theisen and T Henriksen (1983) The accidental dose was determined by using the same type of tablets Exposing them to known doses from 1 to... damages produced by radiation that are relatively permanent One type of damage that fills this requirement is the formation of free radicals in solid matter (clothes, nails, teeth, etc.) In the accident described above, the victim used nitroglycerol tablets because of heart problems He always carried a small box containing these tablets The tablets were irradiated during the accident and rather stable... during the accident received a dose of about 40 Gy Then, measurements were made with a phantom which was placed in the exposure room at the same position as the victim A number of TLDdosimeters were used and it was found that a dose of 40 Gy to the position of the box with the nitroglycerol tablets (in his pocket) yielded an average whole body dose of 22.5 Gy Conclusion: ESR spectroscopy can be used for . Badgastein, Baden-Baden, Marienbad, and Karlovy Vary had radioactivity in their water and were con- sidered to be healthy places. With the use of a jar and some radium salt (Figure 10. 1), the water. natural background radiation) are considered to be very small. The Use of Large Doses Large radiation doses are used for: • Sterilization of medical equipment Co-60 and Cs-137 γ -radiation are used. permission from A.P. Casarett © 2003 Taylor & Francis 122 Radiation and Health Table 10. 1: LD 50 doses Figure 10. 4. Whole-body irradiation results in changes in the number of blood cells. This