Introductory Radiation Biology Exam I, 2005 WHEREVER POSSIBLE, SHOW ALL WORK!!! AND UNITS!!! (NO WORK, NO CREDIT!!!) 1. There is only one NBC affiliate commercial newsroom in the world associated with a university, the MU School of Journalism’s KOMU-TV 8. The station’s broadcast frequency is 183 MHz (1.83 × 108 s-1). What is the energy (in eV) of the “J-School’s” TV news photons? 2. When Dr. Lewis was a postdoctoral fellow at Washington University in St. Louis, he used a cyclotron to produce 6631Ga (T1/2 = 9.5 h) for imaging research. 6631Ga decays exclusively to 6630Zn (stable), with a decay energy of 4.15 MeV. In 50% of events, 6631Ga decays to the ground state of 6630Zn, with emission of a charged particle. In 6% of events, 6631Ga decays to an excited state, 3.23 MeV above the ground state of 6630Zn, with emission of a charged particle. This excited state de- excites in less than 1 ns by two paths: 1) de-excitation to an intermediate excited state 1.04 MeV above the ground state, followed by de-excitation to the ground state (5%), or 2) de-excitation directly to the ground state (1%). a. Sketch a decay scheme that is consistent with this information. b. In the other 44% of events, 6631Ga decays by 1. isomeric transition. 2. electron capture. 3. spontaneous fission. 4. bacterial decomposition. c. Dr. Lewis worked with Professor Mark Green of Purdue University to image tumor folate receptors, using the radiopharmaceutical 66Ga-DF- folate. At the end of a cyclotron run, it took Dr. Lewis 2.5 hours to purify 66 Ga from the target, and it took Dr. Green 1 hour to synthesize 66Ga-DF- folate for injection. A subject was imaged with 4.5 mCi of 66Ga-DF-folate 25 hours later. Assuming no loss of radioactivity during radionuclide purification and radiopharmaceutical synthesis, how much 66Ga did Dr. Lewis need to produce on the cyclotron to accomplish the imaging procedure? d. List all the types of emissions (i.e., photons and particles) that will occur during the decay of 66Ga. 66 3. The linear attenuation coefficient (μ) of the 3.23 MeV Ga photon in lead is 0.395 cm-1. a. What is the half-value layer (HVL) of this photon in lead? b. How many cm of lead are required to reduce the initial intensity (I0) of these photons to a safe level, that is, by 90% (i.e., It = 10% of I0)? c. The thickness of the lead bunker in which Dr. Lewis purifies the 66Ga is exactly 5 cm. Is he safe from 90% of these photons, or does he need to add more lead to keep from getting fried by ionizing radiation? 4. At Duke University, 211At (T1/2 = 7.2 h) is injected into areas where brain tumors have been surgically removed, in order to kill “guerrilla cells” that cause the cancer to come back. The LET of the 6.8 MeV 211At alpha particle (i.e., 42He+2) is 195 keV/μm. a. What is the range of this alpha particle in brain tissue? 1 +1 b. Estimate the LET (in keV/μm) of a 6.8 MeV proton (i.e., 1H ) in brain tissue. 5. TRUE/FALSE _____ a. The wavelength of a 100 keV x-ray photon is longer than the wavelength of a 5 eV ultraviolet photon. 131 _____ b. I is produced by spontaneous fission of 235U, following neutron irradiation in a nuclear reactor. Therefore, it is generally used for radiation therapy. _____ c. Alpha particles are emitted over a wide spectrum of energies, while beta particles (β- and β+) are always monoenergetic. _____ d. Marie Curie won the 1911 Nobel Prize in Chemistry for the discovery of “uranium rays.” _____ e. A 1 MeV gamma ray is more likely to interact with soft tissue by Compton scattering than by the photoelectric effect. _____ f. The ionization density along the linear track of a 1 MeV electron is higher than that along the linear track of a 1 MeV alpha particle. _____ g. The range of 500 keV photons in soft tissue can vary from 0 to , while 500 keV beta minus particles are expected to have approximately the same, relatively short range in soft tissue. _____ h. As the energy of a given type of charged particle increases, its linear energy transfer (LET) decreases. _____ i. The minimum energy required to ionize an atom or molecule is approximately 10 eV. 6. Rank the following forms of ionizing radiation in order of increasing ability to penetrate soft tissue (i.e., range). (Fill in the blanks: rank the least penetrating radiation number 1 and the most penetrating number 6.) a. 1 MeV alpha particle _____ b. 1 MeV proton _____ c. 2 MeV alpha particle _____ d. 1 MeV electron _____ e. 1 MeV gamma ray _____ f. 2 MeV positron _____ 7. The atomic number of a daughter nuclide is the same as that of the parent radionuclide following a. alpha decay. b. beta minus decay. c. positron decay. d. electron capture. e. isomeric transition. 8. By now you might need a little extra energy to finish this exam, so you reach for your thermos and take a sip of hot coffee. It gives you enough energy to a. boost your IQ by 50 points and ace the test. b. raise your blood pressure by 50 points and cause a heart attack. c. kill you if it were ionizing radiation instead. d. make you glow in the dark. 9. Which of the following is considered a high LET radiation? a. a 15 MeV LINAC electron b. a 62 keV tungsten characteristic x-ray c. a 5 MeV alpha particle d. a 573 keV beta minus particle e. all of the above 10. When positrons combine with electrons in matter at the end of their path, what happens? a. They undergo an annihilation reaction. b. They create a particle with twice the mass of an electron but no charge. c. Two 511 keV (0.511 MeV) photons are emitted in opposite directions. d. Both (a) and (c) above. e. Nothing whatsoever. 11. When a radionuclide undergoes beta minus decay, which of the following must occur? a. emission of gamma rays b. creation of an antineutrino c. emission of Auger electrons d. internal conversion e. emission of a positron 12. Briefly define, identify, or describe. a. Wilhelm Conrad Röntgen b. Ionizing radiation c. The atomic mode of energy loss that competes with gamma ray emission d. LET e. Radioactive decay, or radioactivity g. Mean free path INTRODUCTORY RADIATION BIOLOGY EXAM II, 2005 1. A radiation worker in a uranium processing plant received a whole body dose of 1000 rem as a result of an accident. It is estimated that the worker received a 500 rem dose from gamma-rays and the remainder of the equivalent dose received was from fast neutrons. Assuming the QF for fast neutrons is 10: a. Calculate the radiation absorbed dose (in rads) that this worker received from the gamma-ray exposure b. What is the rad dose you calculated in a) expressed in units of Gy? c. Calculate the radiation absorbed dose (in rad units) this worker received from the fast neutron exposure. 2. 250 mrems = _____ mSv. 3. The three most prominent free radicals produced when water is irradiated with high energy gamma-rays are _____________, __________________, and ___________________. 4. The attached semi-log paper figure is a plot of two cell survival curves (Curve A and Curve B). Answer the following questions relating to these survival curves. Assume both survival curves were generating by irradiating human lung cells that were exposed under atmosphere O2 conditions when irradiated using either 1 MeV gamma-rays or 4 MeV alpha particles and at a high dose rate. a. The DO for Curve B is _______ b. The DO for Curve B is (higher than, approximately the same as, lower than) the DO for Curve A. c. The extrapolation number for Curve A is approximately ___________ d. The sensitivity (i.e., k) for Curve B is __________ rad-1. e. Identify which Curve (A or B) would have been generated by irradiation of the cells with alpha particles. f. The D10 for Curve A is ___________ rads. 5. Outline the steps in the Nucleotide Excision Repair process (i.e., cut and patch), and at appropriate steps, identify the enzyme involved. 6. Using the double strand break (dsb) and single strand break (ssb) models, describe how irrepairable damage and induce a permanent genetic mutation to a double strand DNA molecule can occur (sketches will be helpful) by a: a. one hit process b. two hit process 7. Briefly explain (and/or use a sketch) to show why oxygen will not sensitize cells irradiated with high energy protons while it will sensitize those same cells when irradiated at high dose rate with X-rays. 8. Briefly explain why a lower fraction of human cells that are irradiated at a high dose rate with one single 200 rad dose of gamma-rays will die than if the 200 rad dose of gamma rays was delivered in two separate 100 rad doses that were delivered with a one day interval between the first 100 rad dose and the second 100 rad dose. Assume both were delivered at a high dose rate. 9. Briefly explain or define. a. Superoxide anion b. Free Radical c. D50 d. The Roentgen unit e. X-P cells f. sub-lethal damage g. Absorbed dose h. Contrast UV radiation to Ionizing Radiation (e.g., X-rays) i. RBE 10. TRUE/FALSE ___ a. The Roentgen is normally considered an "Equivalent" Dose unit. ___ b. Both the base excision and the nucleotide excision repair processes always result in breakage of the DNA strand to which the damaged base(s) is (are) attached at some point during the repair process. ___ c. A culture containing human lung cells were irradiated under a pO2 = 100 mm Hg with 4 MeV alpha particles at a high dose rate (e.g., 100 rads/min). These cells would be expected to be two to three times more sensitive when compared to these same human line cells irradiated with the 4 MeV alpha particle beams only at a lower dose rate (e.g., 0.1 rads/hr). ___ d. A single nitrogen atom (i.e., 14N) that has zero charge will be a free radical. 7 ___ e. Two different mammalian cell populations [i.e., white blood cells (WBCs) and liver cells] were irradiated with a beam of 10 MeV protons to produce a cell survival curves. The DO for the WBCs was measured to be 50 rads and the DO for the liver cells was 400 rads. The WBCs are more radiosensitive than the liver cells. ___ f. Fast neutrons (e.g., 4 MeV neutrons) will lose a larger percentage of their energy (kinetic), on the average, each time they collide with the nucleus of a calcium nucleus (e.g., 42 Ca), compared to when they collide with the 20 nucleus of a hydrogen atom (i.e., 11 H). NAME___________________________________ INTRODUCTORY RADIATION BIOLOGY FINAL EXAM, 2005 1. A radiation worker received a whole body exposure of 2500 mrads from a beam of fast neutrons. If the QF value for fast neutrons is assumed to be 20; a. What is the equivalent dose (in rem units) this worker received? (Show equation) b. How many Gray (Gy) did this worker receive? 2. a) What is the "oxygen effect"? b) Sketch the typical curve one gets when the OER (Y-axis) is plotted vs. the pO2 oxygen concentration (X-axis) following irradiation of mammalian cells with X-rays. c) You would expect that the OER vs. pO2 curve will be the same if the same cells were exposed to 5 MeV alpha particles (TRUE/FALSE). 3. a) Current estimates are that approximately ___% of the people in the U.S. will contract (get) cancer some time in their lifetime. Approximately ____% of the U.S. population is expected to die from cancer. b) Each person in a U.S. city of 100,000 people received a 2 rem whole body dose from low LET radiation. According to the UNSCEAR 2000 report, approximately ____ people in this city will be expected to die from cancer induced by this radiation exposure (Show Work). c) If scientists studied this population for the long-term, you would expect that this epidemiological study would demonstrate a statistically significant increase in the number of cancers that occurred in this population as a result of the 2 rem per person, exposure (TRUE/FALSE). 4. Explain the differences between "one-hit" and "two-hit" mechanisms for production of "irrepairable" damage to DNA (A sketch will help). 5. Explain the reasons epidemiologists are able to demonstrate measurable increases (i.e., significantly higher than background levels of spontaneous cancers) of radiation induced leukemia and thyroid cancer in mammalian or human populations at lower dose levels (e.g., at 10-30 rem whole body exposures) compared to the higher doses required to demonstrate statistically significant increases in radiation induced lung and colon cancers. Hint, there are two primary contributing factors. 6. a) The reactor accident at Chernobyl in the Ukraine unleashed radioactive fallout that contained 131I-iodide. Studies in populations exposed to high levels of fallout showed that young children (younger than 2-3 years old) experienced radiation-induced thyroid cancers at a rate that was (LESS THAN/ABOUT THE SAME AS/MUCH HIGHER THAN) predicted using previously epidemiological data on 131I-iodide exposure data in adults. 131 b) I-iodide is approved by the U.S. FDA (i.e., about 5-10 mCi orally administered doses of 131I-NaI) for treatment of human patients for hyperthyroidism (a benign disease). Epidemiological studies on patients previously treated for this disease with 131I-iodide show that this treatment significantly (statistically significant) DOES increase thyroid cancer incidence in these patients later in life compared to hyperthyroid patients treated with surgery and no administration of 131I-iodide . 7. List three effects that may occur as a result of in utero exposure of an embryo or fetus at a dose of 75 rads during the first trimester. 8. Briefly explain why there will be less repair of radiation damage to mammalian cells induced by 100 rads by exposure to 2 MeV neutrons compared to exposure of the cells to 100 rads of 1 MeV gamma-rays. 9. Briefly define or describe: a) hydroxyl free radical b) D37 (obtained from survival curves) c) Sublethal damage induced by X-radiation of cells d) The radiation dose to the U.S. population from natural background sources of radiation is _____ approximately mrem. 10. True-False ___ a) There are A FEW types of radiation-induced cancers produced in humans that are not found "spontaneously" in the U.S. population. ___ b) In utero irradiation of the mammalian fetus or embryo DOES produce some specific types of congenital malformation that are NOT found "spontaneously" in newborn babies. ___ c) Epidemiological studies of X-ray and Nuclear Medicine Technologists and Radiologists practicing in the U.S. since 1950 have been unable to demonstrate that this group has experienced measurably (i.e., statistically significant) higher levels of cancers due to their occupational exposures to ionizing radiation. ___ d) The fetus is more sensitive to in utero radiation in the first trimester for production of congenital malformations than in the second and third trimesters. ___ e) Analysis of A-bomb survivor data HAS been able to demonstrate a significant increase in radiation-induced cancers in this population, but HAS NOT been able to demonstrate a significant increase in radiation induced genetic (hereditary) effects. ___ f) "Elkind Repair" is more prevalent (per rad) in mammalian cells exposed to 4 MEV alpha particles (high LET radiation) compared to the same cells exposed to X-rays. ___ g) It is generally agreed by the radiation biology community that a whole body dose of 10 rads or less from low LET radiation is considered to be a "Low Level" radiation exposure. NSEINI 7328 Radiation Biology Final Exam Questions, Dr. Lattimer 1. Which of the following represents the most important chromosomal abnormality induced by ionizing radiation? A. Single strand break B. Nitrogenous base deletion C. Multiple single strand breaks D. Double strand break E. Sulfhydrl cross link deletion 2. Ionizing radiation has different levels of lethality for cells in different parts of the cell cycle. Cell in which phase of the cell cycle are generally considered to be most resistant to killing by ionizing radiation? A. G1 phase B. S phase C. G2 phase D. M phase E. G0 phase 3. Over the years there has been much research conducted into the modification of radiation response using chemicals and drugs to change the lethality of ionizing radiation for cells. Which of the following is the most potent chemical modifier of radiation injury in mammalian cells? A. Oxygen B. Halogenated pyrimidine C. WR 2721 (Amophostine) D. Metronidozole E. Carbon Dioxide 4. Despite the relatively narrow range of radiation sensitivity seen in mammalian cells as determined by clonogenic assays the various organs in the body display a wide range of clinical responses to radiation injury. Which of the following represents the major reason for this apparent disparity? A. Cells in their parent tissues have different susceptibility than those in cell culture B. Cells in their parent tissue have greater ability to repair radiation injury C. Cells in culture do not have access to protective chemicals present in tissue D. Cells in culture are constant cycling whereas those present in tissues may not be. E. Cells in culture are less well supplied with nutrition than those in tissue. 5. There are several mechanisms by which cells injured by radiation may be lost from the cell population. Which of the following is a reproduction related loss which is not necessarily related to mitosis? A. Interphase death. B. Apoptosis C. Extranuclear DNA fragmentation D. Anoxic death E. Metastasis 6. As stated above, in vivo tissues vary widely in their clinical response and susceptibility to killing by ionizing radiation. Which of the following tissues would generally be considered to be most sensitive to ionizing radiation injury? A. Bone marrow B. Lung C. Testicles D. Thyroid E. Embryonic morula 7. Whole body irradiation with penetrating radiation such as gamma rays or neutrons to a uniform whole body dose of 10 gray will almost invariably result in death. Which of the following is the usual cause of death in this case? A. Dehydration B. Blood loss C. Neurological dysfunction D. Systemic infections E. Anemia 8. Tissue and cell response to ionizing radiation is different depending on the level of dose absorbed and even the rate at which the dose is delivered. Which of the following responses is most likely to occur at doses of less than D0? A. Regeneration B. Reoxygenation C. Fibrosis D. Interphase death E. Cellular replacement 9. Tumors vary considerably in their response to ionizing radiation from normal cells for a variety of reasons. Which of the following is one tumor response which is not typically observed in normal tissues? A. Recruitment B. Repopulation C. Reoxygenation D. Repair E. Reassortment 10. Much of radiation oncologic practice centers around the use of multiple small dose of radiation to a tumor rather than a single large dose of radiation to the tumor. This is referred to a dose fractionation and it is done to reduce the effects of the radiation on critical normal tissues in the area of the tumor. Differences between tumor cells and critical normal cells in which of the following account for the success of this approach? A. Recruitment B. Repopulation C. Reoxygenation D. Repair E. Reassortment INTRODUCTORY RADIATION BIOLOGY 7328/4328 FINAL EXAM QUESTIONS 2005—Michael R. Lewis, Ph.D. 1. Rank the following ionizing radiations in order of increasing LET (i.e., beginning with the lowest LET; e.g., a < b < c < d < e, but please note that this may or may not be the correct answer!). a. 500 keV proton b. 5 MeV alpha particle c. 1 MeV beta minus particle d. 140 keV gamma ray e. 500 keV alpha particle 2. Lutetium-177 (17771Lu; T1/2 = 6.65 days) decays to 17772Hf (stable). In 89% of events, 177Lu decays to the ground state of 177Hf, while in 11% of events, it decays to an excited state of 177Hf that lies 208 keV above the ground state, which de- excites in <1 ns to the ground state. a. Sketch a decay scheme that is consistent with this information. b. True or False (circle one): 177Lu decay can be imaged using a gamma camera. c. True or False (circle one): 177Lu cannot be used for radionuclide therapy. d. Dr. Mike Lewis has obtained very promising data evaluating 177Lu radiopharmaceuticals in mouse models of cancer. During one of these experiments (based on a true story), a coworker spilled 177Lu on the floor, Dr. Lewis stepped in it, and he could not clean it off his shoe. How long (in days) did it take for the 177Lu to decay to 0.1% of its original level, so it was safe for Dr. Lewis to wear those shoes again? 3. Briefly define or describe (no more than 1-2 sentences): a. The type of radiation that positron emission tomography (PET) scanners detect b. Half-life of a radionuclide c. Marie Curie d. The radionuclide or radiopharmaceutical used to treat thyroid diseases, like hyperthyroidism and well differentiated thyroid carcinoma e. The most biologically relevant mechanism by which ionizing photons interact with soft tissue (HINT: predominates in the energy range of 100 keV to 10 MeV) TRUE/FALSE 4. _____A 1 MeV alpha particle will have higher LET over its track and greater relative biological effectiveness (RBE) than a 1 MeV beta minus particle. 5. _____18F decays by positron emission, which makes it highly useful for diagnostic imaging, especially of cancer. MULTIPLE CHOICE 6. If a patient shows high uptake of 99mTc-MDP in bone tumors, he or she is potentially a good candidate for therapy with a. Na131I (sodium iodide). 153 b. Sm-EDTMP (QuadraMet™). 201 c. TlCl (thallium chloride). d. all of the above. e. none of the above. 7. [18F]Fluorodeoxyglucose (18F-FDG) accumulates predominantly in brain, heart, and tumors because a. these tissues derive much of their energy from glucose. b. the radiopharmaceutical gets “metabolically trapped” inside their cells. c. these tissues have high rates of glucose metabolism. d. all of the above e. none of the above 8. The component of a gamma camera that defines (or “focuses”) the field of view and ensures that a small part of the detector “sees” only a small part of the organ or tissue being imaged is the a. sodium iodide crystal. b. photomultiplier tube array. c. collimator. d. pulse height analyzer. e. patient bed. 9. Which one of the following agents is not used for physiologic imaging? 18 a. F-FDG. b. diagnostic x-rays. 99m c. Tc-MDP. 201 d. TlCl. 99m e. Tc-Sestamibi. Third Examination NSEI 4328/7328 November 10, 2005 Dr. Lattimer For each of the following questions please indicate the single best response: 1. Cellular DNA is the primary target within the cell for injury by ionizing radiation. Which of the following types of injury is the most easily repaired by cellular repair mechanisms? A. Single Strand Break B. Complementary base pair deletions C. Single nitrogenous base deletion D. Double Strand break E. Sufhydrl exon crosslink deletion 2. Susceptibility of the DNA to radiation injury changes as the cell passes through its various phases of the cell cycle. During which of the following phases of the cell cycle is the DNA most resistant to radiation injury? A. G1 B. G0 C. S D. G2 E. M 3. The DNA is replicated when the cell divides. During which phase of the cell cycle is the DNA actually replicated? A. G1 B. G0 C. S D. G2 4. Relatively low doses of radiation to a cycling cell population may result in a phenomenon known as mitotic delay. During this time there is presumably some repair of radiation injury that is taking place. At what point in the cell cycle does this delay or arrest in progression through the cell cycle occur? A. During G1 Phase B. At the G1-S interface C. During S Phase D. During the G2 phase E. At the M-G1 interface 5. Apoptosis is an important event in radiation biology as it represent perhaps the major way in which cells that have sustained radiation injury are removed from the cell population. At which of the following points in the cell cycle does apoptosis occur? A. During G1 Phase B. At the G1-S interface C. During S Phase D. During the G2 phase E. At the M-G1 interface 6. With regards to the response of tissues to radiation, it is observed that some tissues seem to be more responsive or react more to irradiation than other tissues. This is principally due to differences in which of the following? A. Degree of cell differentiation B. The respective rate at which the cells divide C. The difference in intrinsic sensitivity of the cells to radiation injury D. The differences in the degree of vascularization in the tissues E. The number of stem cells in the tissue 7. Rubin and Casarett’s classification of cell populations on the basis of differences in cellular reproductive kinetics is useful in explaining some of the tissue effects of irradiation. Which of the following cell types is more likely to be associated with tissues exhibiting an early response to irradiation?. A. Vegetative Intermitotic Cells B. Differentiating Intermitotic Cells C. Multipotential Connective Tissue Cells D. Reverting Postmitotic Cells E. Fixed Postmitotic Cells 8. According to the Rubin and Cassertt classification system, liver parenchymal cells (hepatocytes) would classically fall into which of the follow types of cell populations? A. Vegetative Intermitotic Cells B. Differentiating Intermitotic Cells C. Multipotential Connective Tissue Cells D. Reverting Postmitotic Cells E. Fixed Postmitotic Cells 9. Another classification system has be described by Michalowski which groups cells more according to the type of reproductive pattern which is used to replace lost cells. This system also is based principally on reproductive kinetics of the cell population of interest. Which of the following cell types would represent a classic example of a F-type (flexible) cell population? A. Bone marrow stem cells B Intestinal Crypt cells C. Hepatocytes D. Spermatagonia E. Neurons 10. Although classification systems are useful, tissues themselves are usually comprised of multiple cell populations and the effects must be assessed for each cell type and the overall effect on the tissue will probably be associated with the most “sensitive” cell in the tissue required for that tissue to survive. This cell line is know as which of the following? A. The critical cell line B. The determinate cell line C. The dominate cell line D. The early responding cell line E. The late responding cell line. 11. Clonogenic assays have been used for decades to evaluate the sensitivity of many cell lines to ionizing radiation. These assays measure which of the following? A. A cell’s ability to function after irradiation at a given level. B. A cell’s ability to survive after irradiation at a given level. C. A cell’s ability to repair radiation injury after irradiation at a given level. D. A cell’s ability to replicate after irradiation E. A cell’s intrinsic sensitivity to radiation injury 12. Cells are the basic building blocks of most living things on earth. The intrinsic sensitivity of cells to irradiation is different for differ Phyla of organisms. Which of the following has the greatest resistance to injury by ionizing radiation? A. Bacteria B. Fungi C. Oak trees D. Insects E. Mammals 13. The shape of the curve for tissue functional assays is often substantially different than that seen in clonogenic assays. Which of the following explains why? A. Cellular function is less damaged by irradiation than reproductive capability B. Functional capacity is more sensitive to radiation than reproductive capacity C. Tissues often contain a substantial amount of functional reserve D. Functional capacity is often augmented by remote tissues E. Cellular function is not damaged by irradiation 14. There are many different tissues in the body and each of them exhibits its own intrinsic apparent sensitivity to irradiation based on the cell populations present in that tissue. However all tissue share at least one cell type which is the default dose limiting cell type. That cell type is which of the following? A. Fibroblasts B. Red blood cells C. White blood cells D. Vascular endothelium E. Neurons. 15. There are several tissue kinetics factors which impact on the way in which a tissue responds to irradiation. These determine the profile of the response and recovery of a tissue following irradiation. Which of the following is not generally considered a considered a tissue kinetic factor? A. Cell cycle time B. Cell growth factor C. Cell death factor D. Cell oxygenation E. Cell type 16. Acute and Chronic changes in tissue must not be confused with early and late response. Which of the following is a description of what a chronic change is? A. Replacement of the original tissue by fibrosis B. Edema at the site of the irradiation C. Apoptosis of cells in the radiation field D. Repair of cellular injury E. Reoxygenation of the tissue 17. What is seen grossly in the tissue may not be as impressive as the microscopic changes seen in a tissue. Which of the follow would you expect to be the most easily identified clinically? A. Ulcerations on the skin B. Edema under the skin C. Fibrosis of the skin D. Atrophy of the subcutaneous fat E. Thinning and reduction of the blood supply to the skin 18. The blood has complex chemical and cellular makeup. Irradiation has a wide range of effects on the cellular constituents of the blood. Which of the following cell types found in the circulating blood is the most resistant to radiation injury? A. The red blood cell B. Platelets C. Small mature lymphocytes D. Granulocytes E. Monocytes 19. One of the body systems which displays prominent early reaction to irradiation is the digestive tract. It is one of the dose limiting systems that determines whether or not a patient survives a moderate radiation dose to the whole body. Which of the following portions of the digestive system is displays the most severe early changes following irradiation? A. The esophagus B. The stomach C. The small intestine D. The colon E. The oral mucosa 20. The gonads (testicles and ovaries) are one of the organs in the body which dictate the allowable level of occupational exposure to ionizing radiation recommended by the NCRP (National Commission on Radiation Protection). Which of the following effects of gonadal irradiation is a major reason that the annual allowable limit is set at 5.0 Rem? A. Loss of fertility B. Loss of hormonal function C. Mutation induction in reproductive cells D. Cancer induction E. Excessive hormonal production 21. Irradiation of growing bone and cartilage can lead to deformities of the skeleton later in life. At which of the following ages is irradiation of part of the skeleton at levels above 2Gy most likely to result in skeletal growth abnormalities later in life? A. 1-5 years of age B. 5-10 years of age C. 10-15 years of age D. 15-20 years of age E. 20-25 years of age. 22. Total body radiation syndromes are the result of uniform irradiation of all of the major organ systems of the body. This means that the radiation dose is sufficient in all of these areas of the body for significant cell death to occur. It does not preclude the possibility that some parts of the body may get lower or higher doses. At which of the following dose ranges would you expect to begin to see clinical signs from a “total body” irradiation? A. 1-2 Gy B. 3-5 Gy C, 6-8 Gy D. 9-10 Gy E. 11-12 Gray 23. Total body radiation syndromes are really a complex of changes which, if the dose is high enough will result in the death of the patient. Which of the following is most likely to be the disease process which ultimately kills the patient with a whole body dose of 10 Gy? A. Liver failure B. Lung failure C. Brain edema D. Systemic infection E. Dehydration 24. Rapidly growing embryo’s are especially sensitive to radiation injury and will die from doses which are easily sustainable by an adult of the same species. Which of the following explains why. A. Embryonic cells lack the ability to repair minor chromosome damage. B. Loss of only one or a few cells can prevent development of a major organ system C. Embryonic cells undergo anaphase death (like lymphocytes) when irradiated D. Embryonic cells are dividing so quickly there is no time for DNA repair to occur E. Embryos have huge blood supplies and therefore are hyperoxygenated. 25. Following the period of major organogensis (42 days in humans) the overall sensitivity of the fetus to irradiation is somewhat decreased, however significant damage can still occur at very low doses. Which of the following organ systems is most likely to suffer substantial injury following a fetal dose of 20 Rem during this period of fetal growth? A. Heart and Lungs B. Gastrointestinal system C. Central Nervous system D. Reproductive system E. Kidneys and bladder 26. Low whole body radiation doses may not result in any manifest illness however damage to the body may still be detectable by laboratory tests. Doses on the order of 1 Gy to the whole body can significantly impact the function of the immune system. Which of the following immune system functions is lease likely to be affected by a radiation dose of this magnitude? A. Recognition of a foreign antigen presented to the body B. Lymphocyte production by the bone marrow C. Maturation of lymphocytes into plasma cells in the tissues D. Antigen antibody complex phagacytosis my monocytes E. Production of antibodies by the plasma cells. 27. The major application of radiation biology principals today is their application to the performance of radiation therapy for treatment of cancer. Which of the following attributes of cancerous tissue is most likely to contribute to a tumor’s resistance to killing by ionizing radiation. A. The highly heterogeneous phenotype of cells in a tumor B. The primitive or “blastic” nature of tumor cells. C. The accelerated cell cycle time of tumor cells D. The presence of hypoxic cell populations in the tumor E. The lack of “contact inhibition” in tumor cell growth patterns 28. Radiation therapy is one of the mainstays of cancer treatment, particularly for large tumors. Radiation treatment increases the cell loss fraction within a tumor. This is done principally through augmentation of which of the following causes of tumor cell loss. A. Development of hypoxic/anoxic cell populations within the tumor B. Nonviable replication tumor cells C. Immunologic attack on tumor cells by the body’s immune system D. Shedding of tumor cells into the vasculature where they cannot viably exist E. Loss of vascular supply to portions of the tumor 29. Tumor oxygenation is a major issue with regard to the radiocurability of tumors since the hypoxic cells in a tumor may require three times as much dose for sterilization as oxygenated cells. There are however, two different types of hypoxia seen in tumor tissues. Which of the following is a feature of acute hypoxia which is not affected by the radiation dose? A. Release of intratumoral vasospasm B. Death of well oxygenated cells C. Compression of surrounding tissues causing reduce blood flow to the tumor D. Movement of hypoxic cells into a more oxygenated area of the tumor E. Decreased growth potential of vascular channels and endothelium 30. The Four (or five) R’s of radiation biology can be used to explain many of the clinically observed affects of radiation on tumors and normal tissues. Which of the following is an effect which is of very little or not importance in normal tissues? A. Redistribution (reassortment) B. Regeneration (Repopulation) C. Repair D. Reoxygenation E. Recruitment 31. Response to radiation treatment at the tissue level is apparently some what different than that seen with clonogenic assays in a laboratory. Different tissues seem to respond in different ways and to different degrees to irradiation. Differences in which of the following most likely explains this phenomenon? A. Redistribution (Reassortment) B. Regeneration (Repopulation) C. Repair D. Reoxygenation E. Recruitment 32. One of the major effects of fractionated radiation therapy on tumor cell populations is the movement of cells from the non-cycling G0 pool into the cycling cell population. This is referred to as which of the following? A. Redistribution (Reassortment) B. Regeneration (Repopulation) C. Repair D. Reoxygenation E. Recruitment 33. A single dose of radiation to a tumor site has insufficiently different effect on tumor cells from that seen in normal cells to result in significantly more damage to the tumor than the normal tissues so single dose irradiation of a tumor is only applicable if only the tumor and no normal tissue can be irradiated. Otherwise fractionation is employed. Fractionation has the greatest benefit for which of the following:? A. Acute effects in early responding tissues B. Late effects in early responding tissues C. Late effects in late responding tissues D. Acute effects in late responding tissues E. There are no differences for any of the above 34. The effect of fractionation for increasing the effect of radiation on tumors versus normal tissues is different at different doses per fraction and different dose rates. Therefore fraction size is usually chosen at a point on the survival curve which will maximize the effect. Which of the following represents the point on the dose curve which is usually chosen as the approximate fraction size? A. Dq B. D0 C. 10% survival D. 80% survival E. The end of the linear part of the curve 35. There are instances where fractionation of the total radiation dose is not really beneficial in improving tumor control while sparing normal tissues. Which of the following would represent such an instance. A. Treatment of a rapidly growing lung tumor with x-rays B. Treatment of a spinal cord tumor with x-rays. C. Treatment of rapidly growing skin tumor with electrons D. Treatment of a rapidly growing brain tumor with protons E. Treatment of a slow growing skin tumor with gamma rays 36. When treating tumors in areas where the late effects of irradiation on normal tissues are of paramount importance (such as in treating brain tumors), fraction size is a very important consideration. Increasing the number of fractions delivered without increasing the total dose delivered or the time required to deliver the dose to the patient should have which of the following effects? A. Increasing late effects and increasing early effects B. Decreasing late effects and decreasing early effects C. Increasing late effects and decreasing early effects D. Decreasing late effects and increasing early effects E. Decreasing late effects without altering early effects 37. When considering the timing of radiation fraction delivered in multifractionate dose regimes it is important the take into account the effect of repair on the tissue’s response to irradiation. Which of the following is generally considered to be the minimum time one should wait between delivering radiation fractions so that intracellular repair can be complete? A. 1 hour B. 6 hours C. 12 hours D. 18 hours E. 24 hours 38. Many man-years of effort and tens of millions of dollars have be spent in trying to find ways to chemically modify the response of normal tissues and tumors to irradiation with ionizing radiation. Which of the following is the most potent (powerful) chemical modifier of cellular radiation injury? A. Misonidazole B. WR-2721 (Amophostine) C. Halogenated pyrimadines D. Chemotherapy drugs E. Oxygen 39. Hyperthermia has been studied for many years as a means of altering the response of tumors to irradiation therapy in such a way that the tumor is injured more than the normal tissue. There are many attributes of hyperthermia which make it an attractive adjunctive treatment for use in conjunction with radiation therapy. Which of the following is not an effect of hyperthermia on tumor cells which complement radiation treatment. A. Inhibition of intracellular repair B. Increases double strand break formation C. Increases nutritional stress on the cell D. Inhibits formation of, or damages tumor vasculature E. Preferentially kills cell in S phase 40. Brachytherapy has many attributes which make it an attractive means of delivering radiation therapy. However, there are problems with this technique which precludes it being used in many tumors. Which of the following effects represents a major problem with this technique? A. Migration (movement) of the sources after implantation B. Sharp concentration of the radiation dose within the tumor C. The low dose rate reduces the Oxygen Enhancement Ratio for hypoxic cells D. The overall time for administration of the radiation dose is reduced E. The continuos dose of radiation inhibits repopulation of the tumor.