Introductory Radiation Biology Exam I 2009 WHEREVER POSSIBLE, SHOW ALL WORK!!! AND UNITS!!! NO WORK, NO CREDIT!!! 1. In 1986, CBS anchorman Dan Rather was attacked by a man who thought the networks were watching him and sending him signals. As he beat Rather, he kept yelling “Kenneth, what is the frequency?” If the energy of the network signal is 10-3 eV, what is the frequency? 2. 64 29Cu (T1/2 = 12.7 h) is one of only 62 radionuclides that decay by emission of two certain types of charged particles. In 17.4% of events, the maximum particle energy = 655 keV and 6429Cu decays to 6428Ni (stable). In 39.0% of events, the maximum particle energy = 573 keV and 6429Cu decays to 6430Zn (stable). a. Sketch a decay scheme that is consistent with this information. b. The stable isotopes of copper are 63Cu and 65Cu. Therefore, 64Cu 1. 2. 3. 4. is proton rich. is neutron rich. behaves as if it is both proton rich and neutron rich. is an alpha emitter. c. Emission of these two charged particles accounts for 56.4% of 64Cu decay events. In the remaining 43.6% of events, 64Cu decays by 1. 2. 3. 4. d. During the decay of 64Cu, it emits a 1.35 MeV gamma ray in 0.6% of events and an average of only 2 Auger/conversion electrons. Therefore, the majority of the remaining radiation emitted by 64Cu is in the form of 1. 2. 3. 4. e. 3. spontaneous fission. electron capture. isomeric transition. alpha emission. x-rays. alpha particles. neutrons. nuclear recoil. At Washington University in St. Louis, Dr. Carolyn Anderson is evaluating 64CuTETA-octreotide, a tumor-targeting peptide, for diagnostic imaging of cancer. A cancer patient receives an injected dose of 3 mCi, and 60% of that dose is eliminated in the urine within 4 hours, after which no further excretion occurs. How much 64Cu remains in the patient when images are acquired at 6.35 hours post-injection? The half-value layer of the 141 keV 99mTc gamma ray is 0.27 mm in lead. a. What is the linear attenuation coefficient (μ) of this photon in lead? b. How many mm of lead are required to reduce the initial intensity (I0) of these gamma rays by 99.99% (i.e., It = 0.01% of I0)? (Use next page if necessary.) c. Approximately how many half-value layers (HVLs) is this? 4. 5. The range of a 1 MeV proton (11H+) in soft tissue is 23 µm. a. What is the LET of this proton in soft tissue? b. Estimate the LET of a 1 MeV alpha particle (i.e., 42He2+) in soft tissue. TRUE/FALSE _____ a. The range of a 1.33 MeV 60Co gamma ray is shorter than the range of a 15 MeV LINAC electron in soft tissue. _____ b. Radionuclides produced by charged particle accelerators (e.g., cyclotrons) usually decay by positron emission or electron capture, making them useful for diagnostic imaging. _____ c. Beta particles emitted during radioactive decay are always monoenergetic. _____ d. Henri Becquerel won the 1901 Nobel Prize in Physics for his discovery of x-rays. 6. _____ e. As the energy of a given type of charged particle increases, its linear energy transfer (LET) decreases. _____ f. Alpha particles are monoenergetic, while positrons are emitted over a spectrum of energies. _____ g. When a high-energy charged particle (e.g., a 5 MeV alpha particle) collides with an atom in an absorbing medium, it usually transfers most of its kinetic energy to that atom. _____ h. Without knowing the source, one can easily distinguish a 250 keV x-ray from a 250 keV gamma ray, using a conventional radiation detector. Rank the following forms of ionizing radiation in order of increasing range in soft tissue. (Fill in the blanks: rank the least penetrating radiation number 1 and the most penetrating radiation number 6.) a. b. c. d. e. f. 7. 15 MeV electron 2.75 MeV gamma ray 650 keV positron 100 keV electron 5 MeV proton 5 MeV alpha particle In terms of radiation biology effects, the most important mechanism by which photons interact with soft tissue is a. 8. _____ _____ _____ _____ _____ _____ the photoelectric effect. b. Compton scattering. c. d. e. transfer of an average of 60 eV by collision with an atom. pair production. none of the above. You may have heard the story of the “radioactive Boy Scout,” who got busted by the police while trying to build a breeder reactor in his garage, by extracting large quantities of thorium from Coleman lantern mantles and americium from smoke detectors. (This is a true story!) Suppose he succeeded in building his reactor and it underwent a critical “meltdown,” causing him to absorb a lethal dose of radiation. In all likelihood, a. b. c. d. 9. If a CT scanner has a tungsten x-ray tube, the range of its 62 keV photon in soft tissue is a. b. c. d. e. 10. approximately 15.6 cm. highly variable. finite, but impossible to measure experimentally. infinite. none of the above. Anytime a nucleus is capable of emitting a gamma ray, a. b. c. d. e. 11. he would have glowed in the dark until he succumbed to radiation toxicity. the radiation would have immediately induced spontaneous human combustion. he would have preferred to absorb the same amount of energy by drinking one sip of hot coffee. he would have been posthumously awarded the radiation biology merit badge. the gamma ray energy could be imparted to an orbital electron, which is ejected as a conversion electron. it must be undergoing isomeric transition. it must have been left in an excited state following alpha or beta decay. all of the above. none of the above. Briefly define, identify, or describe: a. Ionizing radiation b. Radioactive decay c. LET d. Name one person who discovered or characterized naturally occurring radioactivity. e. Mean free path f. The predominant decay mode of fission and reactor products g. Half-life of a radionuclide Name_________________________ INTRODUCTORY RADIATION BIOLOGY EXAM II – 2009 1. In examining the survival curves as a result of irradiating three different kinds of human cell lines with ionizing radiation, you would conclude that the following statements are TRUE or FALSE. ___a. Curve A was likely to be produced by irradiating the cells under oxygen with 1 MeV gamma rays at a high dose rate. ___b. The D0 for Curve A and B are approximately the same. ___c. Curve C represents cells that are less sensitive to ionizing radiation compared to cells represented by Curve B, assuming both cells in B and C were irradiated under identical conditions with the same type of radiation. ___d. The extrapolation number for Curve B is higher than the extrapolation number for either Curves A or C. ___e. Curve B is representative of killing cells by only a one-hit process. 2. Outline the steps involved in the Nucleotide Excision Repair Mechanism, including the repair enzymes involved in respective steps. 3. Briefly define and/or explain a) Differences between the results deposition of UV radiation (e.g., 260 nm) energy by DNA bases in comparison to results of deposition of energy by ionizing radiation. b) Sub-lethal damage to cells by X-rays. c) Reproductive death d) D0 and how it mathematically relates to the radiation biologist concept of sensitivity. e) X-P cells and their sensitivity to U.V. light compared to cells from normal humans. 4. TRUE-FALSE ___a. Elkind repair occurs to a greater extent in human cells irradiated with fast neutrons compared to when those same kinds of cells are irradiated with 1 MeV gamma-rays. ___b. UV radiation predominantly causes damage to DNA bases (i.e., T, C, G or A) by ionizing those bases following absorption of the UV photon. ___c. During both the Nucleotide and Base Excision Repair Processes for repair of DNA damage, a single strand break is always produced. ___d. Human kidney cells irradiated under O2 with 1 MeV gamma rays at a high dose rate were found to have a D0 = 100 rads. If those cells were irradiated under identical conditions, except at a very low dose rate, you would expect the D0 to be less than 100 rads. 5. A radiation worker received a whole body dose of 50 mrad from fast neutrons (QF = 20) and a whole body dose of 100 mrad from gamma rays. a. Calculate the number of mrem the worker received from the 50 mrad dose of fast neutrons. b. Calculate the total number of mrem this worker received (i.e., from his/her neutron dose plus the gamma ray dose). c. Calculate the number of mSv the worker received from the 50 mrad fast neutron dose. 6. (a) Describe (using a sketch) creation of a double strand break on a DNA molecule by a one-hit process. (b) Describe (using a sketch) how a double strand break on a DNA molecule can be created by a two-hit mechanism. (c) The rate at which the radiation dose is delivered (dose rate effect) will have a greater effect on the rate of cell killing by the one-hit process compared to the rate of cell killing by a two-hit process. ( True / False ) 7. Identify which of the following species/molecules are free radicals. a. b. c. d. H2O O2 H+ H2O2 e. f. g. h. OH OHH “solvated” e 8. Define and explain RBE 9. a) Explain briefly the "Oxygen Effect". b) Explain why this is an important factor in limiting the ability to treat tumors with one dose of high-energy electron beams or x-rays (a sketch may help). 10. Briefly explain or define: a. Free radical b. Why neutrons have high ability to penetrate soft tissue c. How reoxygenation causes tumors to shrink with multiple radiation doses (a sketch may help) d. The free radical most responsible for DNA damage with low LET radiation e. Why a fast neutron will, on the average, lose more of its energy in a single collision with a hydrogen atom nucleus (i.e., a proton) compared to the average amount of energy lost during a single collision with a lead atom nucleus f. 1 Gy = 100 ? g. 1 Sv = 100 ? h. Why a double strand break of DNA is considered a form of irreparable damage 11. TRUE/FALSE a.____ The RBE generally decreases as the LET increases. b.____ Human lung cells in culture were irradiated with 2 MeV protons. These cells were irradiated under an atmosphere where PO2 = 150 mmHg. The OER for these oxygenated cells irradiated with the 2 MeV protons beam is expected to be between 2.5 - 3.0. c.____ High LET radiation causes DNA damage predominantly by direct DNA ionization, while low LET radiation causes most of its damage by indirectly producing free radicals. d.____ An alpha particle needs only one hit to kill a cell, whereas x-rays need hundreds of free radicals to kill a cell. e.____ Ionizing radiation predominantly causes damage to the bases (i.e., T, C, G, or A) comprising DNA molecules by "excitation" (i.e., promoting an orbital electron to higher energy, excited state molecular orbital). f.____ Glutathione is a molecule containing thiol (-SH) groups. You would expect that high levels of glutathione would sensitize cells to ionizing radiation when irradiated with x-rays. g.____ As the LET of a radiation increases, cell sensitivity to damage increases. NSEI 7328 – Introduction to Radiation Biology Exam III November 19, 2009 Dr. Lattimer For each of the following statements please indicate whether the statement is true or false. ______ each cell. ______ ______ mammals. ______ chains. ______ ______ 6. _____ 7. _____ 8. _____ 9. _____ 10. _____ 11. _____ 12. _____ 13. _____ 14. _____ 15. _____ 16. _____ 17. _____ _____ _____ _____ _____ _____ 18. 19. 20. 21. 22. 23. _____ 24. _____ 25. _____ 26. _____ 27. _____ 28. 1. All of the genetic code on the DNA is used to determine the function of 2. 3. The nitrogenous bases of the DNA may be paired in any combination. The number of Chromosomes present in the cell is the same for all 4. The backbone (side rails) of DNA are composed of sugar-phosphate 5. Chromosomes are visible by light microscopy only during Mitosis Direct ionization of the DNA molecule is the principal type of damage caused by low let radiation. Double strand breaks are the most serious type of DNA damage. Replication of the DNA occurs during the G2 phase of the cell cycle. Mitosis is the when the replicated DNA separates into two identical groups of chromosones. Fragments of DNA broken by radiation may not be included in the cell nucleus after division. Acentric DNA fragments in the nucleus are completely non-functional. G0 is the part of the cell cycle where the cell is usually performing its specific function. DNA repair occurs within one hour after the injury to the chromosome. Base excision repair is reliable and efficient. Nucleotide Excision Repair involves both the nitrogenous bases and the DNA backbone. Nonhomologous End Joining repair is a reliable and efficient repair process. Loss of Homologus Recombination repair capability results in increased radiation sensitivity. Single Strand Break Repair is a rapid but error prone process. Cell death at low doses is probably due to isolated double strand break injury. Repair of Potentially Lethal Damage is potentiated by hypoxia. Lethal Damage to the DNA is increased by high LET radiation. Sublethal Damage Repair capability varies with the phases of the cell cycle. Radiation injury to a chromosome during mitosis delays completion of mitosis until repair is complete. Repair of radiation injury is prolonged during S-phase. Reassortment of the cells in the cell cycle is one effect of radiation induce mitotic delay. Decreased efficiency of cell killing is one result of very low dose rate radiation exposure. Repopulation can account for cells lost to Lethal Damage at very low radiation dose rates. High LET radiation results in increased cell killing per unit radiation dose regardless of radiation LET. _____ 29. _____ 30. _____ 31. _____ 32. _____ 33. _____ 34. _____ 35. _____ 36. _____ 37. _____ 38. _____ 39. _____ 40. _____ 41. _____ 42. _____ 43. _____ 44. _____ 45. _____ 46. _____ 47. _____ 48. _____ 49. _____ _____ _____ _____ 50. 51. 52. 53. _____ 54. _____ 55. _____ 56. _____ 57. _____ 58. Most mammalian cells, in cell culture, exhibit the approximately the same level of clonogenic radiation sensitivity, regardless of tissue of origin. Clinically evident differences in tissue radiation sensitivity are tied to cellular division kinetics. Cells that are unable to divide show greater radiation sensitivity than those that can. Undifferentiated cells are the source of increased radiation sensitivity in a tissue. The greatest source of biologic stress on a cell is related to production of enzymes and proteins Skeletal muscle cells and neurons are highly differentiated cells. The cell population classification system of Rubin and Casarett is based on tissue cell reproductive kinetics. In general Vegetative Intermitotic Cell population must be continually replaced. Differentiating Intermitotic Cells are an example of a type of blast cell. Fibroblasts are a type of cell that undergoes proliferation in response to a tissue injury. Cells lining the alveoli (air sacs) of the lung are examples of Reverting Postmitotic cells. Mature plasma cells (antibody producing cells) are examples of Fixed Post Mitotic cells. Perceived radiation resistance of some cells at the tissue level is largely due to their short cell cycle times. Hierarchical cell populations progressively differentiate with each division. Flexible type cell populations are represented by cells like as bone marrow cells. Critical cell populations in a tissue are those that exhibit the most severe reaction to irradiation. Endothelial cells are essentially the “default” critical cell line in some tissues. Late effects after apparent healing following irradiation of a tissue may occur due to critical cells with a long cell cycle time. S-phase cells are generally considered more resistant to radiation injury than G1 cells. Radiation sensitivity increases as cells pass through the G1 phase of the cell cycle. Although cell lines differ in their repair capability the rate of repair is typically the same. Single strand break repair is minimally affected by high LET radiation. Repair is virtually completed by 8 hours after irradiation. Hypoxia is a potent preventer of DNA repair. The survival curves for clonogenic assays and tissue/organ assays in living animals following irradiation yield virtually identical curves. An in vivo assay is one that is performed in cell culture. Clonogenic assays measure cellular functional capacity following irradiation. A control sample is one that is used to measure or compensate for cell loss due strictly to the procedure itself. For an in situ assay the irradiated tissue is allowed to remain in the animal until analysis. Clonogenic assays may not be performed in vivo. _____ 59. _____ 60. _____ 61. _____ 62. _____ _____ _____ _____ 63. 64. 65. 66. _____ 67. _____ _____ _____ _____ 68. 69. 70. 71. _____ 72. _____ 73. _____ 74. _____ 75. _____ 76. _____ _____ _____ _____ _____ 77. 78. 79. 80. 81. _____ 82. _____ 83. _____ 84. _____ 85. _____ 86. _____ 87. _____ 88. Clonogengic assays cannot be performed on RPM and FPM cell lines. Transplantion assays have to be performed in live animals. Functional assays can be used to measure sublethal effects of organ or whole body irradiation. Functional assays are a good way to measure the effects of radiation injury modifiers. Lethality assays are time dependent assays. Chronic tissue changes are the same as late tissue effects. Erythema is an acute tissue reaction to irradiation Acute tissue reactions can be increased by immune system activity in the radiation field. Regeneration and replacement healing after irradiation may occur in the same tissue. Fat loss in a radiation field is an example of a chronic irradiation response. Necrosis may occur in a irradiation field long after apparent healing has occurred. Late responding tissues usually do not undergo acute injury changes. Increasing the volume tissue irradiated will increase the severity of radiation reactions. A large cell cycle growth fraction favors tissue healing by regeneration. Non-cycling cells may be killed by radiation due to death of other cells in the tissue. A 10 gray dose to ½ the bone marrow will reduce circulating white blood cell counts by 50%. Irradiation of the chest in radiation therapy will reduce the patient’s red blood cell count Whole bone marrow doses of up to 8gy can be tolerated without medical intervention. The surface cells of the skin are minimally affected by a radiation dose of 15gy. One potential late effect of skin irradiation is cancer induction years later. Secretory cells in the stomach wall may be critical cells for radiation damage to it. Irradiation of the GI tract may lead to loss of certain hormones in the body. A late effect of severe scarring of the intestine following irradiation may cause death. Special techniques are required to limit radiation dose to the intestine from diagnostic imaging. A dose of 6gy of radiation to the testicles will cause complete loss of testicular function. Loss of ovarian function due to irradiation is the result of death of the oocytes. Viable offspring mutations are a concern with gonadal irradiation of 2.5gy. The retina is very sensitive to radiation injury so dose to it greater than 3gy is likely to result in retinal degeneration. The endothelium is the critical cell in blood vessels with regard to radiation injury. Cardiac irradiation in prolonged fluoroscopic procedures could result in cardiac fibrosis years later. _____ 89. _____ 90. _____ 91. _____ 92. _____ 93. _____ 94. _____ 95. _____ 96. _____ 97. _____ 98. _____ 99. _____100. _____102. _____102. _____103. _____104. _____105. _____106. _____107. _____108. _____109. _____110. _____111. _____112. _____113. _____114. _____115. _____116. Radiation dose from computed tomography is a concern for the bones of young children The kidneys may be potentially at risk from some nuclear medicine procedures. As a whole lung tissue is considered to be relatively resistant to radiation injury. Due to concerns about cognitive development, radiation therapy of the head is avoided in young children if at all possible. For whole body irradiation, the latent stage refers to the period right after the exposure. Whole body irradiation doses above 4gy usually result in vomiting and nausea. The patient recovers following the manifest illness stage after a 10gy whole body dose of radiation. The LD50/60 for bone marrow irradiation is approximately 5gy. In the GI syndrome the principal cause of death is fluid loss into the gut. The LD50/30 for the GI syndrome is the same whether the dose is to the whole body or just the abdomen. Patients exhibiting a CNS syndrome following whole body irradiation invariably die. Patients with CNS syndrome also exhibit severe GI and Bone Marrow syndrome signs. Radiation induce loss of even one cell in an embryo can result in death of the embryo. A 1gy dose to the fetus at 2-6 weeks after conception is unlikely to cause any damage to the fetus. The CNS of a fetus is radiation resistant because the neurons are FPM cells. Fetal irradiation has not been shown to be associated with increased cancer incidence later in life. The low doses of radiation from diagnostic imaging are not considered a risk for a fetus. Although a whole body radiation dose of 1gy may reduce white blood cells numbers it also affects their function. Antibodies are produced by radiation resistant macrophages to kill bacteria in the blood. Death of plasma cells from 1gy of radiation blunts 2o humoral immunity response. Carcinogenic risk from radiation has no lower dose limit. Risk of cancer occurrence following radiation exposure is reduced with time after the event. Tumors can arise from any tissue or organ in the body. Radiation injury to the DNA promotes tumor formation though direct or indirect means. Radiation induced activation of a Proto-oncogene will result in development of a tumor. Tumor suppressor genes antagonize the activity of Proto-oncogenes. Reduced DNA stability gene activity can reduce DNA repair following radiation injury. Up-regulation of Proto-oncogenes frequently involves erroneous DNA repair. _____117. _____118. _____119. _____120. _____121. _____122. _____123. _____124. _____125. _____126. _____127. _____128. _____129. _____130. _____131. _____132. _____133. _____134. _____135. _____136. _____137. _____138. _____139. _____140. _____141. _____142. _____143. Inactivation of a tumor suppressor gene on one chromosome may be transferred to another chromosome. In order to form a tumor a transformed cell must retain its clonogenic capacity. Loss of the p53 gene expression through radiation injury results in increased apoptosis. Tumor growth is promoted by secretion of angiogenic growth factors. Because they arise from normal tissues tumor cells are not at risk from the immune system. Chronic tumor hypoxia is the result of rapid metabolism of oxygen by the rapidly growing cells. Transient hypoxia of all or part of a tumor is caused by vasoconstriction. Radiation results in reoxygenation of the tumor cells by stimulating release of vasoconstriction. The D0 dose of ionizing photons for hypoxic cells is about 4.0 to 5.0 gray. Reoxygenation of tumor cells may result in those cells moving into the cycling pool. Normal tissue tolerance to radiation is dictated by a combination of repair capability, repopulation potential and functional reserve of the critical cell line. Normal tissue tolerance is influenced by affected by irradiated volume and effective dose rate. Generally speaking tumors have shorter cell cycle time than their parent tissue cells. Tumors commonly have cell growth fractions of 10-15%. Anoxic death is a common way in which cells are lost from tumor cell populations. Reassortment of cells in the cycling cell population occurs following irradiation partially because of radiation induced mitotic delay. Malignant tumor cell survival curves exhibit a moderately wide repair shoulder. Radiation doses beyond the repair shoulder can result in less survival of late responding normal cells than tumor cells. Repopulation in normal early responding tissue cells is often greater than in tumor cells. Fractionation of radiation therapy protocols effectively broadens the repair shoulder of normal late responding tissues. Early responding normal tissue cell and tumor cell repair is not affected by fractionation. Early responding normal cells have greater repopulation potential than tumor cells. Increasing the dose per fraction, to reach the same total dose, results in fewer early effects in normal tissue. Reducing the dose per fraction, results in increased spinal cord radiation tolerance. Fractionation effects with high LET radiation are essentially limited to repopulation. Hypoxic cell sensitizer use is frequently limited by their inherent toxicity. Hypoxic cell sensitizers may work indirectly by increasing tumor blood flow. _____144. _____145. _____146. _____147. _____148. _____149. _____150. Radioprotectants improve repair capability of normal cells. Fast neutron irradiation effects on normal tissue cells are not affected by fractionation. Protons are attractive for radiation therapy because their dose to tissues superficial the tumor is low. Hyperthermia acts synergistically with radiation to kill cells in G1 phase of the cell cycle. Hyperthermia is a potent inhibitor of DNA repair. Brachytherapy usually results in high radiation doses to superficial normal tissues. An advantage of brachytherapy implants is that they are difficult to move after placement. Name_______________________________________ INTRODUCTORY RADIATION BIOLOGY FINAL EXAM, 2009 1) List or identify at least three effects that are produced at statistically significant levels as a result of in utero exposure of a human embryo or fetus to a radiation dose of 100 rads from gamma-rays during the first trimester. 2) Briefly explain the reason that it is not possible to demonstrate a statistically significant increase in the number of lung cancers (i.e., reflecting those that could be attributed to exposure to ionizing radiation) in a large population of humans (e.g., an N of 100,000) receiving a radiation dose of 5 rads from a whole body exposure of 1 MeV gammarays. 3) According to the UNSCEAR and BEIR reports handout and discussions during class, it is estimated that approximately _______________ radiation induced cancer deaths will be produced in a population of 1 million people receiving a whole body radiation (low LET) dose of 1 rem each. a) Using this risk estimate and assuming a linear, non-threshold relationship, calculate the number of cancer deaths that would be produced by exposure of a group of 10,000 people given 20 rem of whole body low LET radiation each (show work). 4) Which two of the following cancer types are NOT one of the four most readily (i.e., cancers produced per rem) produced by ionizing radiation in humans. a. lung cancer b. thyroid cancer c. skin cancer 5) d. Kidney cancer e. Leukemia Sketch a cell survival curve produced by irradiating human cells under 02 at a high dose rate with 200 KeV gamma-rays. Label both the X and Y axis. 6) Briefly define or describe a. The base excision repair process b. D0 c. D10 d. linear, non-threshold extrapolation 7) TRUE-FALSE ___ a. There are selected populations of humans that have lived for generations in areas of the world where the natural background radiation is elevated (i.e., approximately 500 mrem/year from naturally occurring radioisotopes present in the soil). It has been shown that the cancer rate is significantly higher in these populations when compared to similar populations living in areas where the natural background radiation levels are not elevated. ___ b. There are some types of cancers that have been shown to be produced specifically (ONLY) by ionizing radiation. Thus, these radiation-induced cancers do not “spontaneously” occur in the U.S. population. ___ c. A slide presented in class and in the accompanying handout provided mortality data of the Japanese A-bomb Survivor Cohort. It showed that by 1990, there were approximately 8,000 total cancer deaths in this cohort population. An estimate of the number of these cancer deaths in this population that could be attributed to the radiation exposure from the A-bomb was also provided. This estimate indicated that approximately half of the 8,000 cancer deaths were caused by the radiation exposure. ___ d. The rate of production (number of effects per rem) of radiation-induced hereditary effects is much higher than the rate of production (number of cancers per rem) of radiationinduced cancers in our population. ___ e. There is a larger percentage of sub-lethal damage that will occur when irradiating cells with 4 MeV alpha particles compared to when the same cells are irradiated with 1 MeV gammarays. INTRODUCTORY RADIATION BIOLOGY 7328/4328 FINAL EXAM QUESTIONS 2009—Michael R. Lewis, Ph.D. 1. Rank the following ionizing radiations in order of increasing linear energy transfer (LET) (i.e., beginning with the lowest LET; e.g., a < b < c < d, but please note that this may or may not be the correct answer!). a. b. c. d. 2. 15 MeV electron 5 MeV proton 250 keV x-ray 6 MeV alpha particle Molybdenum-99 (9942Mo; T1/2 = 66 h) decays to 99m43Tc (T1/2 = 6 h), which lies 141 keV above the ground state and decays to 99g43Tc (T1/2 = 211,100 y). 99gTc finally decays to 99 44Ru (stable). a. b. c. d. Sketch a decay scheme that is consistent with this information. 99m Tc decays predominantly by _______________________________________. True or False (circle one): 99mTc decay can be imaged efficiently by a conventional gamma camera. You are a nuclear medicine physician, and unfortunately your 99mTc generator does not meet Federal guidelines for 99Mo contamination. Therefore, you must obtain 25 mCi of 99mTc-sestamibi, by overnight delivery from Mid-America Isotopes, for a stress test at 9 a.m. on Thursday, December 18. How much 99mTcsestamibi (in mCi) does Mid-America Isotopes have to package at 9 a.m. on Wednesday, December 17, in order for your patient to receive the required injected dose? 3. A radiation worker received a whole body dose of 50 mrad from fast neutrons (QF = 20) and 200 mrad from gamma rays. a. Calculate the number of mrem this worker received from the fast neutron dose. b. Calculate the total dose in mrem this worker received; i.e., neutron dose plus gamma ray dose. c. Which dose (neutrons or gamma rays) has greater relative biological effectiveness? 4. Draw sketches of DNA double strand breaks by one- and two-hit processes. 5. Briefly define or describe (no more than 1-2 sentences): a. A type of radioactive emission used for diagnostic imaging or targeted radiotherapy b. Half-value layer (HVL or X1/2) c. Wilhelm Conrad Röntgen d. Ionizing radiation e. The predominant process by which photons of energy between 100 keV and 10 MeV interact with soft tissue. f. OER g. A DNA-damaging free radical h. How reoxygenation causes tumors to shrink with multiple radiation doses (a sketch may help) i. 100 rem = ? j. RBE TRUE/FALSE 6. _____A 5 MeV alpha particle will have lower LET and cause less biological damage over its track than a 5 MeV β- particle. 7. _____Radionuclides produced by charged particle accelerators generally decay by electron capture and/or positron emission, making them potentially useful for diagnostic imaging. 8. _____Low LET radiation causes most of its DNA damage by “direct hits”, while high LET radiation depends mostly on generation of free radicals. 9. _____As the LET increases, the RBE generally increases. MULTIPLE CHOICE 10. Na131I is useful for treatment of a. hyperthyroid disease. b. non-Hodgkin’s lymphoma. c. differentiated thyroid carcinoma. d. something that needs a radiopharmaceutical. e. both (a) and (c) above. 11. [18F]Fluorodeoxyglucose (FDG) is taken up readily by tumors, brain, and heart, because these tissues a. are interesting to nuclear medicine radiologists. b. exhibit high rates of glucose metabolism and “trap” FDG. c. express abnormally low levels of glucose transporters. d. all of the above. e. none of the above. 12. In order to determine whether a patient with skeletal metastases from prostate cancer is a good candidate to use 153Sm-EDTMP (QuadraMet™) for pain relief, the appropriate diagnostic test is a. imaging with 201TlCl. b. imaging with 18F-FDG. c. imaging with 99mTc-MDP. d. imaging with 99mTc-Sestamibi. e. the number of jumping jacks the man can do. 13. In the future, many diagnostic and therapeutic radiopharmaceuticals for cancer will be targeted by specific binding to molecules, such as receptors or gene products, present in tumor cells. An example of such a radiopharmaceutical is a. Na131I. 99m b. Tc-Sestamibi. 153 c. Sm-EDTMP (QuadraMet™). 18 d. F-FDG. 111 e. In-labeled PNA (peptide nucleic acid). 14. The oxygen enhancement ratio is characteristic of only a. low LET radiation. b. high LET radiation. c. any type of radiation. d. no types of radiation. e. neutrons. 15. An example of a free radical is a. OH· b. OHc. H2O d. H+ e. H2 16. One Gy is equal to a. 1 Sv. b. 100 Sv. c. 100 rad. d. 100 rem. e. 100 neutrons. 17. Which is a form of irreparable damage to DNA? a. single strand break b. double strand break c. no breaks d. base excision repair e. all of the above 18. Which is an example of physiologic imaging? a. MRI b. CT c. planar radiography d. a bone scan using 99mTc-MDP e. none of the above NSEI 7328 Final Questions, Dr. Lattimer - December 2009 1. Which of the following cells is the most susceptible to ionizing radiation? a. b. c. d. e. Bone marrow stem cells Spermatigonia Small circulating lymphocytes Small intestinal crypt cells Vascular endothelial cells 2. Which of the following body systems is generally considered to be most susceptible to radiation injury in a 6 month old human fetus? a. Respiratory system b. Cardiovascular system c. Immune system d. Digestive system e. Central nervous system 3. Which of the following sources of DNA injury is most likely to be repaired? a. Irradiation with neutrons b. Irradiation with photons c. Irradiation with protons d. Irradiaton UV light e. Injury from hyperthermia 4. In which of the following stages of the cell cycle is DNA injury most likely to be repaired? a. G1 phase b. G2 phase c. Prophase d. Telophase e. S phase 5. With regards to the 5R’s of radiation biology which of them is considered to be primarily associated with irradiation of tumors? a. Reoxygenation b. Recruitment c. Reassortment d. Repair e. Repopulation 6. If an individual receives a dose of radiation to his whole body from and external source, which of the following types of radiation would result in the greatest radiobiological effect per Gray of dose? a. Alpha particles b. Protons c. Beta particles d. Neutrons e. Gamma Photons 7. Which of the following tissues is most susceptible to injury by a single dose of ionizing radiation? a. Lung b. Liver c. Kidney d. Skin e. Spinal cord 8. Which of the following classification of tissue cells will usually demonstrate clinically evident response to ionizing radiation first? a. Fixed post mitotic cells b. Reverting post mitotic cells c. Multipotential connective tissue cells d. Differentiating Intermitotic cells e. Vegetative Intermitotic cells Bonus question (5pts) What question did Dr. Lattimer ask most frequently in class??