Radbio

Question 1

The early phases of fibrogenesis after irradiation can be characterized by an upregulation of pro-inflammatory cytokines such as tumor-necrosis factor-α (TNFα) and interleukins 1 (IL1); and what other cytokine?

A. IL2
B. IL6
C. IL10
D. IL15

Answer 1

B. IL6

Mechanistically, the early phases of fibrogenesis after irradiation can be seen as a wound-healing response characterized by an almost immediate upregulation of pro-inflammatory cytokines such as tumor-necrosis factor-α (TNFα), interleukins 1 and 6 (IL1 and IL6) and many growth factors in the irradiated tissue. Chemokines are released and these recruit inflammatory cells from the surrounding tissue into the irradiated volume. IL10 is potent anti-inflammatory cytokine. IL15 is involved in activation of immune cells.

Question 2

Which DNA repair protein functions to promote DNA strand invasion and the search for homology during DNA DSB repair?

A. DNA-PK
B. Artemis
C. Rad51
D. MDC1

Answer 2

C. Rad51

Exposure of cells to ionizing radiation or radiomimetic drugs generates DNA double-strand breaks that are processed either by homologous recombination repair (HRR), or by canonical, DNA-PKcs-dependent non-homologous end-joining (C-NHEJ). RAD51 plays a major role in homologous recombination of DNA strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a template strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process. Artemis is an endonuclease, a protein deficient in a human radiosensitivity syndrome associated with severe immunodeficiency (RS-SCID), in the processing of subsets of DSBs by HRR or C-NHEJ. It is thought that within HRR or C-NHEJ. DNA-PK is a key protein in NHEJ and MCD1 protein is a regulator of the Intra-S phase and the G2/M cell cycle checkpoints and recruits repair proteins to the site of DNA damage.

Question 3

What protein inhibits Cyclin B/CDK1 interaction and inhibits the G2 to M transition after radiation damage?

A. Mdm2
B. Wee1
C. P21-CIP1
D. P27-KIP1

Answer 3

B. Wee1

Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases. Wee1 has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. Wee1 is a tyrosine kinase that is known to be overexpressed in many cancer types such as luminal and HER2-positive breast cancer subtypes, hepatocellular carcinomas, and glioblastomas (Iorns et al., 2009). It regulates the G2-M transition by phosphorylating CDK2 to inactivate the CDK2/cyclin B complex to terminate the cell cycle. The G2 checkpoint is critical for premitotic DNA repair. P21 and P27 are proteins involved in regulating the G1/S phase transition; mdm2 is a protein involved with regulating activation of p53 and the G1/S transition.

Question 4

Combining hyperthermia with radiation is considered a way of targeting cells in which phase of the cell cycle?

A. G1
B. S
C. G2
D. G0

Answer 4

B. S

The two principal rationales for applying hyperthermia in cancer therapy are that: (a) the S phase, which is relatively radiation resistant, are most sensitive phase to hyperthermia, and can be selectively radiosensitized by combining hyperthermia with x-irradiation; the cycling tumor cells in S phase which would normally survive an x-ray dose could thus be killed by subjecting these cells to hyperthermia. For heat shock during S phase, however, the damage in the chromatin is reflected as chromatid aberrations in all the chromosomes. These aberrations apparently induce cell lethality, just as do x-ray-induced chromosomal aberrations.

Question 5

What chemotherapeutic agent leads to DNA chain termination when it becomes incorporated into newly synthesized DNA as the cell replicates?

A. Gemcitabine
B. Mitomycin C
C. Doxorubicin
D. Bleomycin

Answer 5

A. Gemcitabine

Mitomycin C (MMC) is a chemotherapeutic drug that requires an enzymatic bioreduction to exert its biological effects and then leads to Alkylation of DNA is the most favored mechanism of action for MMC, but other modes of action, such as redox cycling and inhibition of rRNA, may also contribute to the biological action of the drug. Plicamycin - RNA synthesis inhibitor. Bleomycin induces strand breaks in DNA. Doxorubicin in an intercalating agent that interacts with DNA by intercalation and inhibition of macromolecular biosynthesis to inhibit the progression of topoisomerase II, an enzyme which relaxes supercoils in DNA for transcription. Gemcitabine is a nucleoside analog, once gemcitabine has entered the cell is becomes phosphorylated and can masquerade as deoxycytidine triphosphate and is incorporated into new DNA strands being synthesized as the cell replicates which leads to “masked chain termination.”

Question 6

What hypoxic cell sensitizer undergoes redox recycling or decomposes to toxic product and has shown efficacy in head and neck cancer?

A. Methotrexate
B. Camptothecin
C. Cetuximab
D. Nimorazole

Answer 6

D. Nimorazole

Nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5–85. (Radiother Oncol. 1998; 46:135–146) showed efficacy in hypoxic tumors. Cetuximab is an inhibitor of EGFR (ErbB family) has have shown to be effective in Head and Neck cancer: Camptothecin is a TOP I inhibitors (poison) involved in cleavage of DNA strands. Methotrexate is a Folic acid analog.

Question 7

Which radiation injury can be evaluated by the crypt stem cell survival assay?

A. Sebaceous gland injury
B. Intestinal injury
C. Serous acini cell injury
D. Eccrine gland injury

Answer 7

B. Intestinal injury

The crypt stem cell survival assay (or microcolony assay) as developed by Withers and Elkind in 1970 is a gold standard to assess the surviving fraction of epithelial stem cells in the small intestine after exposure to high (≥8 Gy) doses of ionizing radiation. The number of surviving crypt stem cells correlates with radiation-induced structural damage in the intestinal wall.

Question 8

What apoptosis-related protein promotes the induction of radiation-induced cell death?

A. Akt
B. Bax
C. Bcl2
D. mTOR

Answer 8

B. Bax

Bax is a pro-apoptotic protein involved in the induction of radiation-induced cell death. Akt, Bcl2 and mTOR promote cell survival.

Question 9

What cellular event activates the ATM protein upon exposure to ionizing radiation?

A. Cell death
B. DNA double strand break formation
C. Mitochondrial respiration
D. Ribosomal assembly

Answer 9

B. DNA double strand break formation

ATM [Ataxia Telangiectasia Mutated], one of the first proteins activated in response to DNA double strand breaks, coordinates several downstream signaling pathway to help the cell respond to the DNA damage.

Question 10

The LD50/30 in an animal radiation model is 5 Gy. When animals are treated with a radiation protector, the LD50/30 is 10 Gy. What is the dose reduction factor of the radiation protector?

A. -5
B. 0.5
C. 2
D. 5

Answer 10

C. 2

The LD50/30 value is the radiation dose that leads to 50% survival 30 days after irradiation. The dose reduction factor can be calculated as the LD50/30 in the presence of the radiation protector divided by the LD50/30 value at baseline. Therefore, with the information given, the dose reduction factor is 10 Gy/5 Gy = 2.

Question 11

What is the biological mechanism by which a superoxide dismutase mimetic protects against radiation injury?

A. By scavenging reactive oxygen species
B. By reducing the absorbed radiation dose
C. By promoting DNA repair
D. By inhibiting inflammation

Answer 11

A. By scavenging reactive oxygen species

Superoxide dismutase (SOD) mimetics reduce cellular oxidative stress, in part by acting as an SOD enzyme and scavenging reactive oxygen species.

Question 12

During RT, a change in what microenvironmental condition can improve tumor control?

A. Decreased tumor oxygen levels
B. Decreased blood flow
C. Increased tumor glucose levels
D. Increased tumor temperature

Answer 12

D. Increased tumor temperature

Locally increased temperatures during radiation therapy (hyperthermia) radiosensitizes many solid tumors. On the other hand, decreasing tumor oxygen levels during therapy or decreasing radiation dose rate may reduce the radiation injury in tumors. Lastly, many tumors are glycolytic, and increased available glucose may promote their growth.

Question 13

Which property of cancer stem cells impact tumor control probability (TCP)?

A. Most prevalent cell type
B. Unlimited proliferative capacity
C. More radiosensitive than other cell types
D. Confer a protective effect on adjacent cells

Answer 13

B. Unlimited proliferative capacity

Mathematical models of TCP are based on a fundamental assumption that tumors contain a population of stem cells that have unlimited proliferative potential that, therefore, must be killed in order to achieve sustained tumor control. Escape of even one stem cell can result in re-population due to this unlimited proliferative capacity.

Question 14

What clinical intervention can reduce the therapeutic ratio of a radiation treatment?

A. Use of a radioprotector that accumulates preferentially in highly vascularized tissues
B. Use of a radioprotector that requires oxygen for conversion from pro-drug to its active form
C. Addition of a selective EGFR-targeted therapy, such as cetuximab
D. Addition of a cytotoxic alkylating chemotherapeutic agent, such as cyclophosphamide

Answer 14

D. Addition of a cytotoxic alkylating chemotherapeutic agent, such as cyclophosphamide

Alkylating agents are cytotoxic, targeting DNA, and tend to be cell-type non-specific. Such an agent would likely result in increased toxicity as well as increased tumor control. The other three responses take advantage of differences between the tumor and normal tissues with respect to molecular biology and/or microenvironment.

Question 15

Why is prostate adenocarcinoma well-suited to hypofractionated RT?

A. Relative to other tumor types, prostate cancer has a high proliferation rate resulting in a large fractionation effect
B. Prostate tumors tend to by hypoxic, and hypofractionation increases reoxygenation compared to conventional fractionation
C. Prostate cancer tends to have a low capacity for repair between fractions, so fewer fractions helps to minimize repair over the course of treatment
D. The alpha/beta ratio of prostate cancer is low, resulting in a large fractionation effect relative to other tumor types

Answer 15

D. The alpha/beta ratio of prostate cancer is low, resulting in a large fractionation effect relative to other tumor types

The majority of prostate tumors are slowly proliferating, resulting in estimated alpha beta ratios of 1-3Gy; lower than other tumor types in which the alpha beta ratios are estimated to be ~8Gy or higher. These characteristics support hypofractionation to achieve higher doses that have been shown to improve tumor control with minimal increase in normal tissue toxicity.

Question 16

How does increasing the number of fractions delivered to a late-responding tissue such as the kidney alter the isoeffective total dose curve?

A. Increases more rapidly than in an early responding tissue
B. Increases more slowly than in an early responding tissue
C. Unaffected by number of fractions
D. Total dose decreases

Answer 16

A. Increases more rapidly than in an early responding tissue

A late responding tissue like the kidney has a low alpha/beta ratio, resulting in a sharper bend in the survival curve (corresponding to a more rapid increase in isoeffective total dose) compared with an early responding tissue in which the alpha/beta ratio would be higher, resulting in a more gradual bend in the survival curve.

Question 17

Which is a mechanism through which hypoxia has been shown to confer resistance to chemotherapy?

A. Activation of mTOR signaling
B. Induction of cell cycle arrest
C. Reduction in cellular adenosine levels
D. Reduction in autophagy

Answer 17

B. Induction of cell cycle arrest

Hypoxia within the tumor microenvironment is associated with cell cycle arrest, allowing the cells to survive in a dormant state and escape the cytotoxic effects chemotherapy.

Question 18

What is the primary mechanism through which taxanes sensitize cells to RT?

A. They promote reoxygenation of the tumor microenvironment
B. They result in cell cycle arrest at the G2/M phase
C. They promote apoptosis
D. They inhibit angiogenesis

Answer 18

B. They result in cell cycle arrest at the G2/M phase

Taxanes’ primary mode of action is to inhibit microtubule formation, thus arresting cells in G2/M phase of the cell cycle, which is the most radiosensitive phase. Taxanes bind to microtubules and, by enhancing their stability and preventing disassembly, adversely affect their function. They act as mitotic inhibitors, blocking cells in the G2/M phase of the cell cycle.

Question 19

Expression of what cell surface marker acts as a “brake” on the immune system and prevents immune cell recognition of tumor?

A. CD20
B. PD-L1
C. HER2
D. EGFR

Answer 19

B. PD-L1

EGFR is a growth factor receptor. Programmed death ligand 1 (PD-L1) is a cell membrane protein that binds to programmed cell death protein 1 (PD-1) on the effector T cells and transduces immunosuppressive signals. It is now clear that the expression of the PD-L1 protein on the tumor cell surface is critical for tumor cells to escape immunosuppression. PD-L1 protein is the functional unit involved in immunotherapy response. PD-L1 is a transmembrane protein that plays a major role in suppressing the immune system. CD-20 is a B-cell marker. HER2/neu is a growth factor receptor.

Question 20

What makes cancer stem cells important targets of anti-cancer treatment?

A. Prevent the development of new secondary cancers
B. Reduces late toxicities of radiation therapy
C. Elevate the repair normal tissue damage
D. They exhibit therapeutic resistance

Answer 20

D. They exhibit therapeutic resistance

Cancer stem cells are pluripotent cells with high replicative potential, resistance to therapy, and ability to repopulate an entire tumor through differentiation. They are thought to be responsible for metastases and may be increased in sites of metastatic disease.

Question 21

What is the percentage of worldwide cancers estimated to be caused by infections?

A. 1%
B. 5%
C. 20%
D. 50%

Answer 21

C. 20%

Worldwide, infections are linked to about 15-20% of cancers.

Question 22

What was a principal conclusion from studies that measured radiation effects on the developing embryo?

A. Irradiation results in macrocephaly
B. Congenital malformations are only seen after 20 weeks gestation
C. The effects are dependent on the gestational age of the embryo
D. Children are heavier and taller than expected

Answer 22

C. The effects are dependent on the gestational age of the embryo

The effects of radiation to the embryo and fetus depend upon the stage of gestation, the dose, and the dose rate. Congenital malformations are seen with radiation in the early (2-6 weeks) phases of development. Severe mental retardation is nearly 4 times more common if the radiation is received between 8 and 15 weeks than if it is received later. Children exposed in utero are shorter, lighter, and have a smaller head diameter than those not exposed to radiation.

Question 23

What agent has been approved as a radiation protector in the event of a radiation emergency?

A. Amifostine
B. Sargramostim
C. Cisplatin
D. Pembrolizumab

Answer 23

B. Sargramostim

Cisplatin is a chemotherapy agent that induces DNA cross linkages; amifostine is used to reduce the side effects of chemotherapy and radiation; pembrolizumab is a antibody therapeutic targeting the immune response to cancer – it has no documented role in radiation protection; none of these compound is approved for use in a radiation emergency. Sargramostim is indicated to increase survival in patients exposed to myelosuppressive doses of radiation.

Question 24

How do the BAD, BID and BIK function in the mechanism of apoptosis cell death?

A. Anti-apoptotic BCL-2 proteins
B. Inhibitor of apoptosis proteins
C. Pro-apoptotic BCL-2 proteins
D. Apoptotic protease activating factor 1 (APAF1) proteins

Answer 24

C. Pro-apoptotic BCL-2 proteins

BAD, BID and BIK are members of the BCL-2 family of apoptotic proteins that have only a single BH3 domain. These proteins induce oligomerization of BAK family members producing pores in the mitochondrial outer membrane, an important step in the intrinsic apoptotic pathway.

Question 25

What assay is used to detect the death of cells by autophagy?

A. X-gal cleavage
B. Western blots of LC3-II
C. Annexin V assay
D. Propidium Iodine uptake

Answer 25

B. Western blots of LC3-II

Modifications of the LC3 protein to LC3-II and its incorporation into the autophagosome are important steps in initiating autophagy.

Question 26

For high dose rate low LET radiations, what does the αD term of the linear quadratic model describe?

A. It describes the formation of a lethal lesion that results from the interaction of two proximate sublesions formed by the same charged particle track
B. It describes the formation of a lethal lesion that results from the interaction of two proximate sublesions formed by two independent charged particle tracks
C. It describes the formation of a lethal DNA double strand break produced by two proximate single strand breaks produced by a single charged particle track
D. It describes the formation of a lethal DNA double stand break produced by the misrepair of two proximate damaged bases produced by a single charged particle track

Answer 26

A. It describes the formation of a lethal lesion that results from the interaction of two proximate sublesions formed by the same charged particle track

The linear quadratic model of cell survival derives from Kellerer and Rossi’s Theory of Dual Radiation Action. This model postulates a linear-quadratic dose response resulting from the interaction of spatially and temporally proximate pairs of “sublesions” to form lethal lesions that kill the cell. In some cases, both sublesions are formed by the same charged particle track. This forms the linear (αD) portion of the curve. The quadratic (βD2) portion results when the interacting sublesions are produced by separate and independent particle tracks.

Question 27

Increasing the dose rate from 0.5 cGy per minute to 1000 cGy per minute will produce what changes in alpha/beta linear quadratic model survival curve parameters?

A. Alpha will increase while beta decreases
B. Alpha will increase while beta increases
C. Alpha will remain the same while beta increases
D. Alpha will decrease while beta increases

Answer 27

C. Alpha will remain the same while beta increases

The alpha-beta survival model is based on the Theory of Dual Radiation Action. This postulates that two proximate sublesions interact to form a lethal lesion which in turn kills the cell. The linear-quadratic (αD + βD2) model for high dose rate low LET radiations has two significant components αD which is linear and results when both sublesions are produced by the same charged particle track. Since are essential formed simultaneously this component is independent of dose rate. The sublesions resulting in the quadratic portion (βD2) of the curve are produced by two independent particle tracks. Here there is a potential for temporal spacing between the two track traversals such that in some cases the first sublesion might be repaired before the second is formed at a later time preventing any interaction. Therefore, increasing the dose rate will have no impact on α but will increase β as the temporal spacing of sublesions formation is reduced increasing the probability of lethal lesion induction via track interaction.

Question 28

Which assumption(s) does the absolute risk model for radiation carcinogenesis make?

A. Radiation risk increases at all ages, as cancer risk increases with age
B. Radiation induced cancer risk is a function of dose and the time since exposure
C. Radiation cancer risk is a function of the square of the dose, gender, and age at exposure
D. Radiation produces an increase in cancer risk over that occurring naturally

Answer 28

D. Radiation produces an increase in cancer risk over that occurring naturally

The absolute risk model assumes any increase in carcinogenic risk will be simply added upon the risk of cancer induction in the absence of radiation exposure. The relative risk model takes age into account as the risk for many cancers increases with age. The time dependent relative risk model treats cancer risk as a function of dose, the square of the dose, age at exposure, and time since exposure.

Question 29

In the DNA damage response, what does γH2AX phosphorylation indicate?

A. Failure of repair complex recruitment
B. Activation of ATM
C. Double strand break resolution
D. Resumption of DNA synthesis

Answer 29

B. Activation of ATM

γH2AX is the phosphorylated form of histone H2AX, and is a phosphorylation target of ATM kinase. After breaks are detected, ATM is activated, H2AX is phosphorylated, and then repair complex proteins are recruited to repair the damage. H2AX is a histone protein, which is rapidly phosphorylated in response to damage to form γH2AX. Staining for the unmodified histone (H2AX) gives a pan nuclear stain or unchanging band on a western blot while γH2AX is rapidly induced on a western blot in response to stress and can be seen to form discreet nuclear foci in damaged cells.

Question 30

Collision of a replication fork with a single strand break induces which cell cycle checkpoint?

A. G1/S
B. Intra-S phase
C. G2
D. M phase

Answer 30

B. Intra-S phase

DNA synthesis occurs in S phase. If a replication fork encounters a single strand break, unwinding of the DNA creates a double strand break, which will activate ATR and an intra-S phase arrest to allow for repair.

Question 31

Which type of chromosomal aberration is MOST LIKELY to be lethal to a cancer cell?

A. Loss of the p arm of a chromosome
B. A balanced translocation
C. Creation of a dicentric
D. Chromosome deletions

Answer 31

C. Creation of a dicentric

Cancer cells often contain chromosome rearrangements, duplications and deletions. Dicentrics however, cannot be properly replicated and will lead most likely to replicative death. The three lethal aberrations are the dicentric; the ring, which are chromosome aberrations; and the anaphase bridge, which is a chromatid aberration. All three represent gross distortions and are clearly visible. The dicentric involves an interchange between two separate chromosomes.

Question 32

Which type of radiation is MOST LIKELY to cause complex chromosomal damage?

A. Gamma
B. UV
C. Proton
D. Carbon ion

Answer 32

D. Carbon ion

High LET radiation causes more complex damage than low LET radiation because of higher levels of localized energy deposition. UV radiation is non-ionizing and causes pyrimidine dimers.

Question 33

Why are normal tissues generally considered to be more radioresistant than tumors?

A. Cells are in the S phase
B. Cells are in the M phase
C. Non-dividing cells in G0 phase
D. Proliferating cells in G1 phase

Answer 33

C. Non-dividing cells in G0 phase

Most “normal” cells remain in a non-mitotic G0 phase, which is radioresistant because cells (non- hematopoietic) tend to die by mitotic catastrophe during cell division. The radiosensitivity of a population of cells varies with the distribution of cells through the cycle. In general, cells are most resistant in late S phase; slowly growing cells with a long cycle, however, may have a second resistant phase in the early G1 phase, which may be termed G0 if the cells are out of cycle. Thus, two quite different cell populations may be radioresistant.

Question 34

How could the effectiveness of a densely ionizing charged particle with an LET of 1000 keV/μm be increased to increase cell killing?

A. Fractionate the dose
B. Decrease the LET to 100 keV/μm
C. Decrease the dose rate
D. Decrease oxygenation of the tissue to 3mm Hg

Answer 34

B. Decrease the LET to 100 keV/μm

An LET of 1000 keV/μm is past optimal LET for DNA damage and thus maximal RBE (occurring at ~100keV/μm), and so decreasing the LET of the ion would increase RBE. Moreover, RBE for densely ionizing charged particles is little affected by dose rate in general; decreasing dose rate would not increase RBE. 3 mm Hg is 0.5% oxygen, and at that concentration the relative radiation sensitivity is ~midway between aerobic and hypoxic conditions so decreasing oxygenation would lower radiosensitivity and thus not increase RBE. Fractionation, would not increase RBE.

Question 35

What effect would REDUCING tumor hypoxia have on cellular radiosensitivity to X rays?

A. Decrease the OER
B. Increase HIF1α activity
C. Lower free radical-induced DNA damage
D. Lower D0 parameter of cell survival curve

Answer 35

D. Lower D0 parameter of cell survival curve

The goal of lowering tumor hypoxia would be to lower the OER of x rays so that cell kill occurs at a lower dose, thus achieving a lower D0. Increasing HIF1α activity would indicate increased hypoxia, not lower, and in that condition radiosensitivity would not be improved; lowering free radical induced DNA damage would not occur by lowering tumor hypoxia (increasing oxygen concentration) nor would it improve radiosensitivity.

Question 36

What explains the increase in cell survival observed when successive 2 Gy fractions are delivered 6 hours apart rather than 1 hour apart?

A. Increased repair of sublethal damage
B. Induction of hypoxia via HIF1 activity
C. Decreased radical-induced DNA damage
D. Reassortment of cells from resistant cell cycle phase

Answer 36

A. Increased repair of sublethal damage

The fluctuation of survival times observed during the course of a split dose experiment is due to reassortment of cycling cells in to portions of the cell cycle having different radiosensitivites. So an increase in survival time that occurs during the course of a split dose experiments is a result of reassortment into a more radiation resistant phase of the cell cycle, such as S, which has a higher capacity for sublethal damage repair. Hif1 activity would indicate a decrease in hypoxic conditions, which would lower cell survival, as would an increase in free radical induced DNA damage (typically occurs in more oxic conditions).

Question 37

What biological characteristic describes sublethal damage repair (SLDR) and cell survival?

A. The α component of LQ model of cell kill
B. Repair of damage in the G2/M portion of the cell cycle
C. A linear survival curve with no shoulder
D. Repair is complete 6 hours after irradiation

Answer 37

D. Repair is complete 6 hours after irradiation

SLDR is generally complete by 1-2 hours in culture. The β component of cell kill, and therefore the shoulder portion of the cell survival curve, best represents repair capacity; the α component best describes cell death as being an exponential function of dose (within limited repair). SLDR capacity is greatest during the dividing portions of the cell cycle, such as S phase.

Question 38

Which is an advantage of carbon ions versus protons?

A. Increased normal tissue sparing
B. Higher LET
C. Spread out Bragg peak
D. Higher OER

Answer 38

B. Higher LET

A radiobiologic advantage of carbon ions relative to protons is a greater LET, which results in increased cell kill. However, because of the high LET and RBE at the Bragg peak, repair capacity of normal tissues is reduced. As a result, sparing of normal tissues with fractionation is lower. For both protons and carbon ions, clinicians can take advantage of a spread-out Bragg peak for tumor treatment. Protons have very similar OER to conventional X-rays, whereas carbon ions have a lower OER than both protons and X rays.

Question 39

Which radiolysis product of water is responsible for approximately two thirds of DNA damage caused by the indirect action of ionizing radiation?

A. H2O2
B. e aq-
C. H2O+
D. OH radical

Answer 39

D. OH radical

Approximately 2/3 of the damage caused by the indirect action of radiation is attributed to the hydroxyl radical, OH-radical. Very little damage is caused by the hydrated electron, e aq-, hydrogen peroxide, H2O2, produces predominantly single-strand breaks and excited water, H2O+, is short-lived and leads to the production of OH . Direct and indirect actions of radiation. In direct action, a secondary electron resulting from absorption of an x-ray photon interacts with the DNA to produce an effect. In indirect action, the secondary electron interacts with, for example, a water molecule to produce a hydroxyl radical (OH·), which in turn produces the damage to the DNA. The DNA helix has a diameter of about 20 Å (2 nm). It is estimated that free radicals produced in a cylinder with a diameter double that of the DNA helix can affect the DNA.

Question 40

Which interactions of ionizing radiation with biological tissues is MOST important in PET?

A. Photoelectric effect
B. Pair production
C. Compton scattering
D. Photodisintegration

Answer 40

B. Pair production

Pair production requires a photon energy of 1.02 MeV which is the energy required to produce an electron (511 keV) and positron (511 KeV) pair. The positron combines with an electron producing two 511 keV photons that are emitted at 180o to each other and are detected in a PET scanner. The photoelectric effect occurs when a a low energy photon interacts with the electron in the atom and removes it from its shell and the incident photon is completely absorbed in the process. The effect is dependent on atomic number of the absorber and is of fundamental importance in x-ray imaging. Compton scattering occurs due to the interaction of the x-ray or gamma photon with free electrons or loosely bound outer shell electrons. The resultant incident photon gets scattered and imparts energy to the electron (recoil electron) and is the predominant effect for therapeutic radiation. Photodisintegration occurs when a high energy photon is absorbed by a nucleus resulting in immediate disintegration of the nucleus.

Question 41

Which cellular assay would be appropriate to use for quantitative measurement of DNA double strand breaks immediately after exposure to ionizing radiation?

A. Neutral comet assay
B. Alkaline elution
C. Western blotting
D. Incorporation of bromodeoxyuridine

Answer 41

A. Neutral comet assay

The neutral comet assay is used to measure DNA double-strand breaks. Alkaline elution is used to measure single-strand breaks and some base damages. Alkaline conditions separate the two DNA strands so single strand breaks are measured in each strand. Western blotting is for detection of proteins, and bromodeoxyuridine incorporation is used as a radiosensitizer or for cell kinetic analysis.

Question 42

What genomic mechanism does NOT result in the activation of a proto-oncogene?

A. Chromosome translocation
B. Methylation of the promoter region
C. Point mutation altering the function
D. Retroviral activation

Answer 42

B. Methylation of the promoter region

Methylation is a process that results in “silencing” of the gene by making it inaccessible to transcription factors. Chromosome translocation is a common process that activates proto-oncogenes such as C-MYC. Point mutations are responsible for the activation of proto-oncogenes such as RAS. Oncogenes were first discovered due to their incorporation into retroviruses.

Question 43

What cellular process is considered a “hallmark of cancer”?

A. Promotion of growth suppressors
B. Immunogenesis
C. Disabling replicative immortality
D. Inducing angiogenesis

Answer 43

D. Inducing angiogenesis

It is widely accepted that cancer cells require unlimited replicative potential in order to generate macroscopic tumors in contrast to the behavior of the cells in most normal cell lineages which are able to pass through only a limited number of successive cell growth-and-division cycles. Angiogenesis is the recruitment of new blood vessels to regions of chronically low blood supply and is essential for the progression of solid tumors to malignancy. Increasing evidence supports the hypothesis that tumor angiogenesis is controlled by an “angiogenic switch,” a physiologic mechanism involving a dynamic balance of angiogenic factors that include both inhibitors and inducers. Numerous angiogenic factors have been identified, including specific endothelial cell growth factors (e.g., vascular endothelial growth factor, or VEGF), cytokines and inflammatory agents (e.g., tumor necrosis factor α, or TNF-α, and interleukin-8, or IL-8), fragments of circulatory system proteins (e.g., angiostatin and endostatin), and ECM components (e.g., thrombospondins, or TSPs). Presumably, this diversity of angiogenic factors reflects a strict requirement for controlling angiogenesis under normal physiologic conditions and in response to oncogenic events by modulating the expression of both angiogenic inducers and inhibitors.

Question 44

Which of the following is NOT a tumor suppressor gene?

A. p16
B. RB
C. SRC
D. PTEN

Answer 44

C. SRC

Cell immortalization can be viewed as a competing process that requires both the activation of dominant activating oncogenes to induce proliferation and the loss of recessive tumor suppressor genes that induce a cell cycle arrest in response to this constitutive activating signal. Tumor suppressor genes act as negative growth regulator, such as PTEN, p16 and Rb which are involved in restricting growth and cell cycle regulation. The product of the human SRC gene, c-Src, has been found to be over-expressed and highly activated in a wide variety of human cancers and has an influence on the development of the metastatic phenotype. It was one of the first proto-oncogenes discovered as a retroviral gene (v-src) responsible for the development of tumors in chickens. p16 is a tumor suppressor gene associated with familial melanoma, RB is a tumor suppressor whose inactivation is associated with retinoblastoma and PTEN is a tumor suppressor gene which inhibits PI3K signaling and its loss of function is common in prostate cancer.