Hebron University - Palestine 37.2. Mechanisms of Cell Damage ■ Ionizing radiation causes damage to molecules, occasionally by a direct hit on a molecule, but more often indirectly by the creation of ‘free radicals’ جذور حرة. ■ Free radicals are uncharged atoms or fragments of molecules possessing an electron. Free radicals may cause damage to cellular proteins by breaking molecular bonds and renderingجعل protein molecules non-functional غير ف ع ا لةor even harmful ض ارة. If there are many undamaged copies of the protein, this may not adversely affect cellular function, but too much damage may result in cell death. ■ Direct hits and free-radical production by radiation may damage cellular DNA. If this occurs there are several possible outcomes: • DNA damage which the cell can detect and fix ي تم إصالحه. • DNA damage that cannot be fixed ال ي تم إصالحه, causing the cell death. • Non-lethal damage ض رر غير ق اتلthat is passed on as a mutation in subsequent cell divisionsي تم ن قله ك طفرة ف ي انقسامات لخاليا ا لالحقة. ا ■ In addition, neighbouring cells ا لخاليا ا لمجاورةwhich are not directly damaged by radiation may experience damage by communication with the damaged cells . DNA damage is described as either somatic جسديor genetic . Somatic damage is noninheritableال ي ورث. ■ The serious adverse effect ا لتأثير ا لسلبيا لخطيرof somatic damage is to increase the risk that a cancer will develop. Genetic damage is inheritable and results from the mutation of DNA in the reproductive ا لخاليا ا لتناسليةcells, and these changes may thus be passed on to future generationsا ألجيا ل ا لقادمة 37.3. Dose and Dose Equivalent (a) The absorbed dose, D, is a physical quantity which quantifies the amount of energy absorbed by some material. • The SI unit of absorbed dose is the gray (Gy). 1 gray is equivalent to 1 joule of energy being delivered to 1 kilogram of matter. An older unit of absorbed dose is the rad. Where 1Gy = 1 J kg−1 = 100 rad The absorbed dose is given by:
where ΔE is the energy lost from the radiation beam, and m
is the mass of material into which the energy is absorbed. • Absorbed dose is an important concept, since the effect of radiation on biological tissue depends directly on the amount of energy absorbed by that tissue. • The damaging effects of radiation occur when molecular bonds in important biological molecules are broken or when free radicals ا لجذور ا لحرةare formed. Both of these processes require energy, and thus the amount of damage produced by radiation is proportional to the amount of energy from the radiation that is absorbed. (b) Dose Equivalent (DE) • The dose equivalent can be thought of as an expression of the dose in terms of its biological effect. To estimate this, we define the relative biological effectiveness (RBE) of a particular kind of radiation (also known as the Quality Factor, Q). The RBE varies from one kind of radiation to another and quantifies the damage produced by each kind of radiation in biological tissue. • Approximate RBE values (summarized from ICRP (1991)) ♦ X and Gamma rays, RBE = 1 ♦ Electrons, RBE = 1 ♦ Neutrons, RBE = 5 ♦ Protons, RBE = 5 ♦ Alpha Particles, RBE = 20 • RBE is a weighting factor عاملت رجيحwhich depends on the type of ionising radiation. The RBE is higher for radiation types that deliver their energy to a smaller number of cells. • The fact that the range of the α particle is less than that of β, γ or X-rays, results in α radiation depositing its energy in a smaller area. • The greater concentration of ionization and cell damage results in greater (adverse) biological effect, and thus a larger value of the RBE. Similarly, β radiation has a larger value of the RBE than γ radiation. • The RBE of γ radiation is set at 1. This means that radiation with a RBE of 7 (for example) is seven times as damaging as the same absorbed dose of γ radiation. • The dose equivalent is measured in Sievert (Sv). The dose equivalent is obtained by multiplying the absorbed dose by the RBE Sv ≡ Gy × RBE • The non-SI unit still in use is the rem (which stands for Röentgen equivalent man): dose equivalent in rem = absorbed dose in rad × RBE, where 1 Sv = 100 rem (c) Effective dose : It is the tissue-weighted sum of the dose equivalent in all tissues and organs of the human body and represents the stochastic health risk ا لمخاطر ا لصحية ا لعشوائيةto the whole body, which is the probability of cancer induction and genetic effects, of low levels of ionizing radiation. E = ∑ WT × DE • Where E: is the effective dose to the entire organismis ل لكائنا لحيك امال
DE the equivalent dose absorbed by tissue
WT is the tissue weighting factor Example 37.1 Page 395 (a) A 5 g tumour ورمis irradiated with high energy X-rays and absorbs a total of 0.2 J of energy. What is the absorbed dose in gray and rad, and the dose equivalent in sievert and rem? (b) An alternate treatmentعالج ب ديلfor the same tumour is to administer a chemical solution containing a radioactive isotope which is preferentiallyب شكلت فضيليabsorbed by the tumour. If the isotope involved ا لمعنيis an alpha emitter with an RBE of 20 and the tumour absorbs 0.05 J of energy. What is the absorbed dose in gray and rad, and the dose equivalent in sievert and rem? Example 37.2 Page 396 Careless 75 غير مبا ليkg radiopharmacologist accidentally ب ا لخطأingests a small amount of a 1.7 MeV Beta emitter with a half-life of 24 days. The activity of the sample ingested is 13 mCi. What is the equivalent dose in rem received by the pharmacologist in the first minute of his exposure to the radioactive sample, if 20% of all beta particles emitted are absorbed in his body? 37.4. Types of Effect ■ Biological effects from ionising radiation have already been categorised as somatic جسديor genetic in terms of the effect of this radiation on DNA. The biological effects of radiation can also be divided into two other categories: deterministic حتميةand stochastic عشوائية. ■ Deterministic effects are produced by radiation doses that are high enough to denature ت دنيproteins or to cause cell death. These effects are therefore definite, noticeable and fairly immediate ل حظية وفورية,محددة. When the radiation dose is smaller, there may not be any obvious damage to cells or organs, but the risk of a disease like cancer is increased. • There are a number of characteristics of deterministic and stochastic effects of radiation exposure: 1- These are early effects: they appear very quickly after the radiation dose is received. 2- They are the result of ‘lethal damage ’أضرار مميتةto tissue. The cells of the tissue are killed by the radiation exposure. 3- The killing of cells by radiation is extensive enough ب ما ي كفيthat it reduces or destroys ي دمرat least some organ function. 4- The lethal damage required to produce cell death occurs only for radiation exposure which results in doses above some minimum value, i.e., there is a ‘threshold’ dose below which deterministic effects do not occur. 5- These verity of these effects increases with increasing dose. • Some examples of deterministic effects are the formation of cataracts, infertility ا لعقمand erythema (skin reddening). These are all the result of cell death in the organs concerned. Stochastic effects, because they can only be discussed in terms of increased risk of disease or of inheritable mutation حدوثطفرة ورائية, are much harder to definitely characterise ي صعبوصفها. However, they are distinct from deterministic effects in several ways: • These are ‘late’ effects ت أثيراتمتأخرة, they do not appear immediately, but occur some time after the radiation exposure has occurred . • They are effects caused by cellular or DNA damage, but damage which is not immediately lethal غير ق اتلعلىا لفور. • The fact that a cell, while damaged, is not killed by radiation exposure means that the cellular repair mechanisms come into operation. • The probability of harm ا لضررincreases with increasing dose. 37.5 . Medical Effects and Risk Large radiation doses may cause radiation sickness. Radiation sickness is referring to a group of deterministic effects which have been observed to appear soon after very large radiation doses. The first symptoms of radiation sickness to occur are typically: Nausea, vomiting, diarrhoea and fatigueا لغثيانوا لقئوا إلسها لوا لتعب. Other symptoms that may occur are skin burns (حروقا لجلدredness, blistering)احمرار وتقرحات, weaknessض عف, fainting إغماء, dehydrationجفاف, anemia ف قر دم, dry coughس ع ا لجاف, inflammation of exposed areas تهاب لمناطقا لمكشوفة ( ا ل اalong with redness احمرار, Tenderness رقة, swelling ت ورم, bleeding)ن زيف, hair loss, ulceration of the oral mucosa ت قرح ا لغشاء ا لمخاطيل لفم, ulceration of the esophagus ت قرح ا لمريء, stomach or intestines ت قرح ا لمع دة وا ألمع اء, vomiting blood ت قيء دم, bloody stoolsب راز دموي, bleeding from the nose, mouth, gums, and rectum,ن زيفمنا ألنف وا لفم وا للثة وا لمستقيم,bruisingك دمات, open sores on the skin ف تح ا لقروح ف يا لجلدand headache ا لصداع. • The cells that are most susceptible ا ألكثر عرضةto death from radiation are those in the intestinal lining ا لموجودة ف يا لبطانة ا لمع وية, white blood cells خاليا ا لدم ا لبيضاءand the cells that make red and white blood cells. Many of the symptoms listed, such as dehydration, vomiting, and diarrhoea, are the result of damage to the intestinal tract مثلا لجفاف، ا لع ديد منا ألعراضا لمذكورة تلف يا ألمع اء هين تيجة ل ف،وا لقيء وا إلسها ل. • The time taken for a person to die ي موتfrom a lethal radiation dose is around two to four weeks. Patients who receive a high full-body dose of radiation and are still alive عاشafter six weeks are likely to recoverمنا لمرجح أني تع افى. ■ The treatments available are largely aimed at ameliorating the symptoms: antinausea drugs, painkillers, antibiotics to help fight infections and blood transfusions for anemia. أدوية مضادات:يهدف توفر العالجات المتاحة إلى حد كبير إلى تحسين األعراض والمضادات الحيوية للمساعدة في مكافحة االلتهابات ونقل، ومسكنات األلم، األيلينا
الدم لفقر الدم
■ Exposure to smaller amounts of radiation may cause no noticeable effects at the time. Long-term epidemiological studies دراسات لوبائية ا لطويلة ا المد ا ا لon populations exposed to varying doses of radiation, such as atom-bomb survivors in Hiroshima and Nagasaki, suggest that the probability of developing cancer from radiation exposure increases linearly with the accumulated dose ا لجرعة ا لتراكمية. 37.6. Ultraviolet Radiation • Ultraviolet radiation (UV) is the part of the electromagnetic spectrum between the violet end of the visible part and X-rays. • Exposure to ultraviolet radiation may well result in damage to biological tissue, but it is not dangerous in the same way as γ or X- ray radiation. • Ultraviolet (UV) photons are those in the wavelength range between X-rays and visible light, around 10 nm to 400 nm. The most important source of ultraviolet radiation in everyday life is the Sun, which emits radiation from wavelengths of about 200 nm up. This range, the ‘near UV’ is subdivided into three categories: UVA – 400 nm to 320 nm. UVB – 320 nm to 280 nm. UVC – 280 nm to 200 nm. • All three types of ultraviolet light reaching the Earth’s surface will damage collagen in the skin, causing premature aging ش يخوخة مبكرة. The least harmful is UVA. UVB on the other hand, causes the most skin reddening (erythema) and can cause DNA damage by disrupting covalent bonds ت عطيلا لروابط ا لتساهميةwhich can lead to skin cancer, and also causes cataracts. • Short - wavelength UV radiation can be used for antibacterial sterilisation ا لتعقيم ا لمضاد ل لبكتريا, as it causes DNA damage that can inhibit the ability of bacteria to replicate ي منع ق درة ا لبكتريا علىا لتكاثر. • Sunscreen ingredients protect the skin in one of two waysواقيات لشمس ا ت حميا لبشرة ب طريقتين – by blocking (reflecting) the UV light (titanium dioxide is a common ingredient in sunscreens of this kind), – by absorbing and re-radiating the energy at much longer wavelengths (avobenzone, does). Problems Page 400 37.1. A 65 kg person undergoing a series of X-rays receives a dose of 12 rem. (a) What dose does he receive in sieverts and rad? (b) How much energy was deposited in the person’s body?
37.3. A person is exposed to ionizing radiation which
deposits 10 J of energy in their tissue. (a) What dose (in Gy) would an 80 kg adult and a 15 kg child receive under these circumstances? (b) What dose (in rem) would the adult and child each receive if the radiation were low energy (< 0.03MeV) β radiation? (c) What dose (in Sv) would the adult and child each receive if the radiation were low energy α radiation? (RBE=10.) 37.4. A person with lymphoma receives a dose of 35 Gy in the form of γ radiation during a course of radiotherapy. Most of this dose is absorbed in 18 g of cancerous lymphatic tissue. (a) How much energy is absorbed by the cancerous tissue? (b) If this treatment consists of 15 minute sessions per week over the course of 5 weeks and just 1% of the γ photons in the γ ray beam are absorbed, what is the power of the γ ray beam? 37.5. A 60 kg person accidentally ingests a small source of alpha particles (RBE=15). The activity of the source is 0.04 Ci, the half life of the source is 110 years, and each alpha particle emitted has an energy of 0.586 MeV. It takes 12 hours for the alpha source to pass through the persons digestive system and exit the body. (a) How many alpha particles are absorbed by the person (you may assume that 100% of the alpha particles emitted by the source are absorbed by the person)? (b) How much energy is deposited in the person by the source (in J)? (c) What is the absorbed dose (in rad)? (d) What is the absorbed dose (in rem)? 37.6. A radioactive contaminant gives an unfortunate 0.5 kg lab rat a dose of 1500 rem in just 1 minute. Assuming that the half life of the radioactive isotope in the contaminant is much longer than 1 minute, what would the activity (in Bq) of the contaminant be if ... (a) the contaminant is a 5MeV alpha emitter (RBE = 15)? (b) the contaminant is a 1.1MeV beta emitter? (c) the contaminant is a 0.01MeV gamma emitter?