ROBex 2020 Flashcards
2020-A1. The biological effects of radiation are dependent upon:
A. Only total dose
B. Total dose, dose-rate, and radiation quality
C. Only dose rate
D. Only dose rate and radiation quality
E. None of the above
Answer: B
The biophysical properties of radiation, including dose rate, ionization density, and total dose are all important determinants of radiation action on cells
2020-A2. Which radiation would produce energy depostions in cells that would result in the most lethal molecular damage?
A. 100 keV electron
B. 1 MeV photon
C. 10 MeV photon
D. 1.0 keV electron
E. 1 MeV neutrino
Answer: D
Low energy or track end electrons deposit their energy over relatively small volumes
2020-A3. The majority of the energy received by biologic material from x rays is transferred by:
A. Electrons
B. Degraded gamma photons
C. Protons
D. Spallation products
E. Neutrons
Answer: A
When x-rays are absorbed in biologic material, the photon first interacts with an orbital electron of an atom of the material by the photoelectric or compton process to produce a fast recoil electron.
The energy of this electron is lost through interactions with other atoms or molecules to produce bio molecular ions. The ensuing biochemical events may or may not lead to biologic effect.
Protons and spallation products are formed when neutrons are absorbed in tissue.
2020-A4. A photon with energy of 100 MeV encouters a calcium atom; identify likely interactions in order of probability:
A. Pair production > Compton scatter > Photoelectric absorption
B. Pair production = Compton scatter > Photoelectric absorption
C. Compton Scatter > Pair production > Photoelectric absorption
D. Photoelectric absorption > Compton Scatter > Pair production
E. Compton scatter > Photoelectric absorption > Pair production
Answer: A
Note that 100 MeV is a high energy photon. This favors pair production, especially in a high Z atom (Ca has a relatively high atomic number for biologic tissues).
By contrast compton scatter is important in intermediate energy photons - from hundreds of KeV to 10 MeV and photoelectric absorption is favored in lower energy interactions
2020-A5. Free radicals produced from the radiolysis of cellular water:
A. are formed primarily in the cell nucleus
B. play a minor role in the oxygen effect
C. contribute to both the “a” and “b” mechanism of cell killing
D. do not play a role in the cell killing by high LET radiations
E. typically exhibit “lifetimes” of approximately 10 seconds
Answer: C
The free radicals produced from the radiolysis of water molecules play a role in both the “A” (single track producing 2 breaks) and the “b” (2 tracks each producing a single break) mechanisms of cell killing.
Water radicals are formed randomly throughout the cell. A large component of oxygen modifiable damage in cells is produced by OH-.
Water radicals are involved in cell killing by both low-LET and high-LET radiations. The lifetimes of free radicals are on the order of microseconds.
2020-A6. It is known that oxygen levels strongly influence the indirect effects of radiation damage. Which observations would you expect in the following studies?
A. cells irradiated under hypoxic conditions exhibit higher levels of DNA strands by x-ray than serobic cells
B. cells grown under aerobic conditions exhibit higher levels of DNA strand breaks induced by low-LET radiation than cells irradiated in hypoxia
C. equal numbers of DNA strand breaks are observed in cells grown under aerobic or hypoxic conditions following treatment with low LET radiation
D. oxygen enhances the toxicity of high LET radiation but has less of an effect on low LET radiation
E. none of the above
Answer: B
High oxygen tensions >10 mm Hg are effective in producing much higher levels of DNA damage than in low oxygen tension
2020-A7. Ionizing radiation produces a number of lesions in DNA. The specific type of radiation-induced DNA damage that is most closely correlated with cell kill is:
A. DNA double stranded breaks
B. DNA single stranded breaks
C. Base damage
D. DNA protein crosslinks
E. Sister chromatid exchange
Answer: A
Unrepaired DNA double stranded breaks are potentially lethal lesions
1 Gy ->
40 DSBs
1000 SSBs
2020-A8. Which one of the following statements is true concerning formation of strand breaks?
A. Single strand breaks are the most common lesion formed by ionizing radiation
B. UV irradiation forms primarily double strand breaks
C. DNA double strand breaks are repaired by mismatch repair
D. Single strand breaks are the most cytotoxic lesions formed by ionizing radiation
E. DNA double strand breaks are repaired in S-phase
Answer: A
Single stranded breaks are the most common lesion formed by ionizing radiation but the yare not the most cytotoxic lesion
2020-B1. According to the linear quadratic model of cell survival, beta-type damage to the DNA molecule means that:
A. Irreparable single strand breaks are produced by the passage of single charged particles
B. Irreparable double strand breaks are produced by the passage of a single charge particle
C. Irreparable double strand breaks are produced by the passage of 2 charged particles
D. Repairable single strand breaks are produced by the beta particles emitted after photonuclear interactions
E. Irreparable double strand breaks are produced by the beta particles emitted after photonuclear interactions
Answer: C
Beta type interactions refer to interactive single strand breaks caused by independent charged particles. Each is considered reparable but when they combine to produce a double strand break, irreparable damage can occur
2020-B2. Clustered lesions in DNA:
A. include strand breaks but not base damages
B. decrease in complexity with increasing LET
C. are more readily and accurately repaired than base damages
D. are produced because of the nanometer scale in-homogeneities in energy depositions in DNA from ionizing radiation
E. are not relevant for cell survival after exposure to ionizing radiation
Answer: D
Clustered DNA lesions (multiply damaged sites) which are produced because of inhomogeneous energy depositions in DNA, include base damages and strand break (and presumably cross-links, although those have not yet been measured).
Clusters increase in complexity with increasing LEt and are important for cell killing because they are more difficult to repair accurately than single lesions.
2020-B3. Irradiation of mammalian cells with 1 to 5 Gy can produce the following types of damage (which one of the following is true):
A. both blunt and staggered double strand DNA break
B. a higher frequency of double strand DNA breaks relative to single strand DNA breaks
C. DNA protein crosslinks
D. significant de-naturation of various proteins
E. Both A & C are true
Answer: E
Both direct and indirect action of radiation can produce an array of blunt and staggered DSBs.
Single strand DNA breaks are always generated at much higher frequency than double strand breaks. Although less frequent than SSB and DSBs, DNA protein crosslinks can be detected after 1-5 Gy of irradiation.
Protein de-naturation requires extremely high radiation doses.
2020-B4. It is known that oxygen levels strongly influence the indirect effects of radiation damage. Which observation would you expect in the following studies?
A. cells irradiated under hypoxic conditions exhibit higher levels of DNA strand breaks by x-rays than aerobic cells.
B. cells grown under aerobic conditions exhibit higher levels of DNA strand breaks induced by low-LET radiation than cells irradiated in hypoxia.
C. equal numbers of DNA strand breaks are observed in cells grown under aerobic or hypoxic conditions following treatment with low LET radiation.
D. oxygen enhances the toxicity of high-LET radiation but has less of an effect on low-LET radiation.
E. none of the above
Answer: B
High oxygen tensions >10 mm Hg are effective in producing much higher levels of DNA damage than in low oxygen tension
2020-B5. Which type of DNA damage listed below is formed by UV radiation?
A. Pyrimidine dimers
B. Double strand breaks
C. Single strand breaks
D. Interstrand bross-links
E. B&C
Answer: A
Pyrimidine dimers are formed by UV radiation
Note: Xeroderma Pigmentosum is linked to a nucleoside excision repair deficit in removing these pyrimidine dimers.
Mnemonic: “X” pigmentosum is “Nude” excision repair
2020-B7. Following irradiation with 3 Gy of 250 kVp x-rays, the number of:
A. single strand DNA breaks > double strand DNA breaks > altered DNA bases
B. altered DNA bases > single strand DNA breaks > double strand breaks
C. double strand DNA breaks > altered DNA bases > single strand DNA breaks
D. altered DNA bases > double strand DNA breaks > single strand DNA breaks
E. single strand DNA breaks > altered DNA bases > double strand DNA breaks
Answer: B
Following a dose of 1 Gy, per cell:
- >1000 base damages
- 800 ssDNA breaks
- 40 dsDNA breaks
2020-C1. Which of the following gene protein products is involved with homologous rejoining?
A. rad50, rad51, and rad 57
B. rad59, rad51, and MRE11
C. XRCC1, MRE11, rad50
D. ku70, rad51, MRE11
E. Only rad50, rad51, and ku70
Answer: A
Several gene products are associated with repair.
Homolorous repair requires the below and other proteins to recognize, signal, and initiate repair of DNA damage:
- rad 50, rad 51, rad 52, rad 54, rad 55, rad57
- ATM, XRCC2, XRCC3, NBS1, and MRE 11
Remember that the MRN complex is MRE11, rad50, NBS1 - this recognized dsDNA breaks
2020-C2. Which techniques are used to characterize DNA repair?
A. Southern blot analysis
B. Alkaline/neutral filter elutions
C. Comet assay
D. Pulsed-field gel electrophoresis
E. All of the above
Answer: E
Southern blotting was used to detect preferential DNA repair of active compared to inactive genes. Mnemonic: SNOW DROP (Southern-DNA, Northern-RNA, Western-Protein)
Alkaline/neutral filter elutions are used to detect single and double strand DNA breaks respectively. (Alk = ssDNA, Neutral = dsDNA) . Mnemonic - To be neutral, you need to see both sides
The comet assay is an electrophoresis separation of DNA fragments from whole cells and thus measures strand breaks
Pulsed field gel electrophoresis (PFGE) is used to separate DNA pieces of relatively high molecular weight. The technique essentially measures dsDNA breaks and can measure repair if cells are exposed to radiation and then allowed to recover over time.
2020-C3. With regard to cell survival after 1.8 Gy of X-rays, which repair process is the least important?
A. Homologous re-combinational repair
B. Base excision repair
C. Mismatch repair
D. Non-homologous end joining
E. Single strand annealing
Answer: C
Mismatch repair does not play a role in the repair of ionizing radiation induced DNA damage
2020-C4. Which process is almost never involved in the repair of DNA damage induced by ionizing radiation:
A. Ligation
B. Recombination repair
C. Double strand break repair
D. Base excision repair
E. Nucleotide excision repair
Answer: E
The nucleotide excision repair pathway primarily repairs UV photoproducts. Little occurs after ionizing radiation as evidenced by the relatively small amount of repair synthesis detected after exposure.
2020-C5. Which repair pathway is responsible for repair for DNA double strand breaks in the G1 phase of the cell cycle:
A. Mismatch repair
B. Interstrand cross-link repair
C. Nucleotide excision repair
D. Non homologous end joinging
E. Homologous recombination
Answer: D
NHEJ is responsible for primarily repairing dsDNA breaks in the G1 phase.
Homologous repair is primarily reponsible for repairing dsDNA breaks in S-phase
2020-C6. Which one of the proteins is involved in nucleotide excision repair?
A. Ku 80
B. DNA PKs
C. ERCC1
D. BRCA1
E. RAD51
Answer: C
ERCC1 is involved innucleotide excision repair
Ku80 is part of the ku70/80 dsDNA repair complex for NHEJ
DNA-PKcs are also used in NHEJ for dsDNA break repair. breaks. DNA-PKcs knockout mice have severe combined immunodeficiency due to their V(D)J recombination defect.
BRCA1 protein interacts with RAD51 during repair of dsDNA breaks (BRCA2 also interacts with RAD51)
2020-C7. Of the following, the DNA repair mechaism that most often results in a mutation is:
A. Non-homologous end joining
B. Mismatch repair
C. Nucleotide excision repair
D. Homologous recombination
E. Base excision repair
Answer: A
NHEJ involves the direct rejoining of free DNA after the removal of damaged nucleotides and therefore nearly always results in the loss of some DNA sequence
2020-C8. Which protein is necessary for NHEJ?
A. BRCA1
B. RAD51
C. XLF
D. MRE11
E. NBS1
Answer: C
Non-homologous end-joining factor 1 (NHEJ1) is also known as Cernunnos or XRCC4-like factor (XLF). It is required for NHEJ.
XLF interacts with DNA ligase IV and XRCC4 and is thought to be involved in the end-bridging or ligation steps of NHEJ.
BRCA1 and RAD51 work together in both HR and NHEJ for dsDNA repair
MRN complex (MRE11/rad50/NBS1) works in initial processing of dsDNA breaks for either HR or NHEJ. The MRN complex also participates in activating the checkpoint kinase ATM in response to DNA damage.
2020-D1. Two hit aberrations:
A. Increase linearly as a function of dose
B. do not exhibit a dose rate/ dose fractionation effect
C. decrease in frequency with increasing dose rate
D. account for the “b” coefficient of dose response curves
E. result from single lethal hits
Answer: D
Two hit aberrations (or DNA breaks) are dependent on the square of the dose; hence they are the “b” component of the dose response curve and will decrease with dose fractionation or decreasing dose rate, both of which allow time for repair.
2020-D2. Which type of chromosome aberration predominates following exposure to low doses of ionizing radiation?
A. Dicentrics
B. Translocations
C. Rings
D. Terminal deletions
E. Interstitital deletions
Answer: D
Single hit kinetics predominates at low doses of ionizing radiation. Terminal deletions involve a single dsDNA break and therefore follow single-hit kinetics.
All of the other chromosome abberations listed involve 2 dsDNA breaks and therefore follow 2 hit kinetics.
2020-D3. Measurement of which one of the following chromosomal aberrations in peripheral blood lymphocytes many years following a putative whole body radiation exposure would provide the best estimate as to the dose received?
A. Reciprocal translocations
B. Rings
C. Dicentrics
D. Chromosome breaks
E. Chromatid breaks
Answer: A
Reciprocal translocations are relatively stable and therefore can be detected at long times after exposure to ionizing radiation.
All of the other chromosome aberrations are highly unstable and therefore can be detected only for a few cell generations at most after exposure before the irradiated cells or their progenitors die.
2020-D4. Which of the following types of chromosomal aberrations is the most likely to cause lethality?
A. insertion
B. dicentric
C. translocation
D. inversion
E. none of the above
Answer: B
The formation of a dicentric chromosome is most likely to trigger the events during mitosis that lead to mitotic catastrophe and the death of the cell (although it should be noted that some dicentrics are stable and long-lived)
The other chromosomal aberrations listed are not as likely to result in cellular death. For example, inversion, translocations, and insertions do not produce acentric gragments.
They could potentially play an important role in carcinogenesis if the portion of the chromosome altered results in the inactivation of a tumor suppressor gene or activation of an oncogene.
2020-D5. Which of the following chromosome aberrations detected a few days to weeks after total body irradiation are useful to reconstruct dose exposures?
A. Rings
B. Dicentrics
C. Deletions
D. Symmetric translocations
E. A and B
Answer: E
In blood samples obtained for cytogenetic evaluation within a few days to weeks after total body irradiation, the frequency of asymmetric aberrations (dicentrics and rings) in the lymphocytes reflects the dose received.
2020-D6. X-ray induced chromosome aberrations:
A. are most often expressed in quiescent cells
B. are produced primarily by direct effects following x-irradiation
C. that involves a symmetrical exchange are generally not lethal
D. are of the chromatid type when cells are irradiated in the G1 phase of the cell cycle
E. such as dicentric and ring chromosomes, are stable
Answer: C
A symmetrical translocation positions genetic information on different chromosomes but usually doesn’t interfere with its expression.
Many other chromosome aberrations, such as dicentric chromosomes and acentric fragments, usually result in lethality when cells attempt to divide.
X-rays produce damage by indirect action.
Chromatid aberrations result from irradiation of cells in late S or G2.
Dicentric and ring chromosomes are unstable aberrations
2020-D7. Which of the following is not true about inversion?
A. Inverted chromosomes are generally viable
B. Inversion can cause chromosome breakage
C. Two DNA strands with an inverted segment will not pair
D. Inversions including centromere is known as para-centric
E. Non of them
Answer: C
Two DNA segments in inversion will pair but the pairing will be via formation of a loop such that appropriate gene loci can come close
2020-D8. Which of the following statements is false?
A. Chromosomal aberrations can lead to cell killing, mutation, or carcinogenesis
B. The ring aberration and the dicentric aberration are chromatid aberrations that are lethal to the cell
C. The anaphase bridge is a chromosomal aberration that is lethal to the cell
D. Symmetric translocations and small deletions are chromosomal aberrations that are not lethal but they can cause malignancies
E. All of them
Answer: B
Only the anaphase bridge is a chromatid abberation.
Most chromosome aberrations lead to cell death. Prime examples of inevitably lethal aberrations:
- Ring chromosome
- Dicentric chromosomes
- Anaphase bridge (chromatid aberration)
Prime examples of chromosomal aberrations, potentially non-lethal:
- Symmetric translocations
- Small deletions
Note that all of these radiation-induced aberrations require two double-stranded DNA breaks.
2020-E1. Which one of the following statements falsely concludes this sentence? Apoptotic cell death induced by ionizing radiation:
A) can occur in both tumor and normal tissues
B. is indistinguishable from necrotic cell death
C. is characterized by chromatin condensation and nuclear fragmentation
D. is initiated within a few hours afer treatment
E. may be heterogeneously expressed within the same tumor
Answer: B
The process of apoptosis involves chromatin condensation, cleavage of the DNA by endonucleases and cell shrinkage. In contrast, the process of necrosis is associated with cell swelling and lysis and can be distinguished from apoptosis by histology and other assays.
2020-E2. When a mammalian cell is irradiated, its probability of survival is reduced. Within the cell, different organelles are differentially damaged by the radiation. Which organelle is generally regarded as the most important in relation to cell survival after irradiation?
A. Plasma membrane
B. Nuclear membrane
C. Mitochondria
D. Golgi apparatus
E. None of the above
Answer: E
The DNA in chromatin is considered to be the primary radiation target in cells
2020-E3. What roles in regulating the intrinsic pathway of apoptosis are played by the Bcl-2 protein family members Bax and Bcl-2?
A. Bax inhibits apoptosis while Bcl-2 stimulates apoptosis
B. Bax stimulates apoptosis while Bcl-2 inhibits apoptosis
C. Both Bax and Bcl-2 inhibit apoptosis
D. Both Bax and Bcl-2 stimulate apoptosis
E. None of the above
Answer: B
The intrinsic apoptotic pathway is tightly regulared in mammalian cells by 2 groups of proteins, one favoring apoptosis and the other inhibiting it. They all belong to a single protein family the Bcl-2 family.
Bax and Bad are pro-apoptotic members of the family and are believed to be inbolbed in the intial formation of pores in the mitochondrial membrane.
Bcl-2 (the first discovered member) and Bcl-xL are important anti-apoptotic proteins that prevent pore formation and cytochrome C release. Whether a stimulus that cuases cell stress produces cell destruction will therefore depend on the balance between the pro-apoptotic and anti-apoptotic proteins.
2020-E4. Which of the following proteins is a death receptor which triggers the extrinsic pathway of apoptosis?
A. Caspase 8
B. FADD
C. Fas
D. Fas ligand
E. p53
Answer: C
The Fas protein is a member of the tumor necrosis factor receptor super family.
Killer T cells, which are able to signal target cells to undergo apoptosis, carry on their surface a protein complementary to Fas called the Fas ligand. When this binds to Fas on a target cell, it stimulates the initiation of apoptosis.
First an adaptor protein, the Fas activated death domain (FADD) binds to the cytosolic domain of the Fas receptor
Procaspase-8 then binds as a cluster to the FADD-receptor complex and is activated by cleavage. Once active, caspase-8 is formed and a proteolytic caspse cascade ensues, leading to activation of the same effector caspases as in the intrinsic pathway.
2020-E5. Concerning radiation induced apoptosis, which of the following statements is incorrect?
A. Disruption of the plasma membrane is a relatively late event in apoptosis.
B. A cell type with a pro-apoptotic tendency is generally radiation sensitive.
C. Apoptosis usually stimulates an inflammatory response
D. Single apoptotic cells are often seen in tissues
E. High levels of bcl-2 inhibit apoptosis
Answer: C
Apoptosis does not stimulate an inflammatory response
2020-E6. During apoptosis, which of the following process(es) is (are) observed to occur:
A. There is a rapid increase in intra-nuclear calcium that activates an endonuclease that digests nuclear DNA to nucleosome multimers
B. The cell ultimately rounds up, shrinks, and may slough off or be phagocytosed by neighboring cells
C. There is an increase in transflutaminase activity that acts to destroy cell integrity
D. There is no immediate loss of cell membrane integrity and very little cell debris leading to minimal inflammation
E. All of the above
Answer: E
All of the statements A-D are characteristic of apoptosis
2020-E7. Autophagy is:
A. an un-regulated process
B. a fusion of ribosomes with autophagosomes
C. the basis of accelerated proliferation following irradiation
D. a process to eliminate damaged proteins or organelles
E. a caspase dependent process
Answer: D
Autophagy or type III programmed cell death is a tightly regulared, ordered cell death process that is a response to nutrient deprivation, hypoxia, crowding, sensence and genotoxic stress such as radiation.
It is a mechanism to eliminate damaged proteins or organelles. Cells that undergo excessive autophagy are induced to die in a non-apoptotic manner as organelles and other cell components are sequestered in autophagosomes that fuse with lysosomes causing degradation of the autophagosomal contents (self-digestion).
2020-E8. The irreversible cell cycle arrest resulting from the loss of telomere function in mammalian cells is called:
A. apoptosis
B. replicative cell death
C. G0
D. mitotic catastrophe
E. replicative cell senescence
Answer: E
Cell senescence is a p53/p16 dependent permanent cell cycle arrest that occurs in some cell types in response to telomere loss. All of the other choices either involve cell death or a reversible (G0) exit from the cell cycle.
2020-F1. Which of the following methods would represent the best way to assess the ability of radiation to decrease the survival of actively dividing cells following irradiation?
A. clonogenic assay
B. division delay
C. apoptosis levels at 24 hours
D. giant cell formation
E. detection of necrotic cells
Answer: A
The most appropriate approach to assess cellular survival to radiation for an actively dividing population of cells is to determine what fraction of the irradiated cells is capable of clonogenic survival (colony formation).
Division delay would measure the amount of cell cycle perturbation caused by radiation, but occurs in all actively dividing cells regardless of whether they ultimately live or die.
Apoptosis is just one form of death and can occur at many different times after irradiation.
The formation of giant cells with multiple nuclei is a manisfestation of cells undergoing mitotic catastophe following the formation of chromosome aberrations but is not the only mechanism of radiation induced cell death.
Likewise, detection of necrotic cells would only provide the graction of cells that undergo this form of cell death and would not give an overall sense of cellular lethality that could also occur through apoptosis, autophagy, mitotic catastrophe or senescence.
2020-F2. Which of the following statements is true concerning the irradiation of a series of cell lines derived from breast carcinomas with an X-ray dose of 4 Gy?
A. Most cells will die within several hours
B. Annexin V staining will be detectable in the majority of cells within minutes
C. A majority of cells will undergo apoptosis before completing mitosis
D. Cells derived from tumors with a mutant p53 (TP53) are radioresistant
E. Many cells will continue to divide for several days
Answer: E
It is likely that following a dose of 4 Gy, many cells that may be reproductively dead will still be able to divide for several days following irradiation until they undergo mitotic catastrophe
It would be anticipated that a minority of carcinoma cells would undergo apoptosis and exhibit annexin V staining. NOTE: In flow cytometry, annexin V is commonly used to detect apoptotic cells by its ability to bind to phosphatidylserine, a marker of apoptosis when it is on the outer leaflet of the plasma membrane. MNEMONIC: “A for A”
Possession of a mutation in P53 would likely not substantially affect the radiosensitivity of carcinoma cells.
It is only tumor cells such as lymphomas that have a pronounced pro-apoptotic capacity for which a p53 mutation results in radioresistance (since the apoptotic pathway is inhibited in these mutant cells).
2020-F3. According to classical target theory, D0 is a measure of the:
A. amount of sub-lethal damage a cell can accumulate before lethality occurs
B. total number of targets that must be inactivated to kill a cell
C. dose required to produce an average of one lethal lesion per irradiated cell
D. width of the shoulder region of the cell survival curve
E. total number of hits required per target to kill a cell
Answer: C
In classical target theory, the “D0” is the dose that reduces cell survival to 37% of some intial value as measured on the exponential portion of the radiation survival curve. The “D0” dose also produced an average of one lethal lesion per cell in a population of irrdiated cells; this can be derived from a Poisson distribution in which there is an average of one lethal hit in a series of targets.
In this instance 37% of the targets will not receive a lethal hit and will survive. It is the quasi-threshold dose, “Dq” which is an approximation of the total amount of sub lethal damage that a cell can accumulate before lethality occurs.
The extrapolation number “n” represents the total number of targets that must be inactivated (or hits that must be recieved in a single target) for a cell to be killed.
The “Dq” would be a manisfestation of the width of the shoulder of a survival curve.
2020-G1. With respect to radiation survival curves of cells, which of the following statements is false?
A. As dose is reduced, the linear quadratic equation asymptotically apporaches an initial slope defined by the “a” value
B. Fitting survival data to the single hit, multi target equation usually underestimates cell killing at low dose
C. Differences in the intrinsic cell sensitivity is expressed mainly as difference in “a” coefficient
D. Differences in the intrinsic cell sensitivity is expressed mainly as difference in “b” coefficient
E. Split dose recovery is predicted by the “b” coefficient
Answer: C
Mammalian cells exhibit large (up to 100x) variations in “a”-coefficients and much smaller (up to 3x) variations in “b” coefficients.
2020-G2. An asynchronous population of cells (G1= 50%, S = 30%, G2-M = 20%) is exposed to 2 Gy X-rays. Immediately after exposure the percentage cell cycle distribution among the cells that will survive is:
A. unchanged
B. increased in G1 and G2/M phase cells
C. decreased in S phase cells
D. increased in S phase cells
E. decreased equally in all phases
Answer: D
Cells in radiosensitive phases of the cell cycle will be selectively killed leaving an increased proportion of resistant S-phase cells that survive
2020-G3. Approximately how many cells will survive in a tumor containing 109 clonogens after a fractionated treatment to a total dose of 40 Gy, assuming the effective D10 is 5 Gy?
A. 0
B. 101
C. 102
D. 105
E. 10<span>8</span>
Answer: B
Each 5 Gy reduces the level of survival by a factor of 10. Therefore 40 Gy will result in a surviving fraction of 10-8.
Since tumor initially containted 109 cells, it is anticipated that 101 will survive.
2020-G4. In the linear-quadratic survival curve model, lnSF = -aD-bD2, “a” is best described as:
A) equivalent to the D0 in the single hit multi target model
B. an indicator of repair potential
C. a measure of the initial slope of the survival curve
D. equal to “b” when the a/b ratio is fixed
E. equal to the recripocal of SF2
Answer: C
The “a” defines the initial slope of the survival curve
2020-G5. All of the following statements are true with respect to in vitro radiation survival curves, except:
A. As dose is reduced, the linear quadratic equation asymptotically approaches an initial slope defined by the “a” value
B. Fitting survival data to the single hit, multi-target equation usually underestimates cell killing at low doses
C. Differences in intrinsic radiosensitivities of tumor cells are expressed mainly as differencesi nthe “a” coefficient
D. Tumors with a pro-apoptotic tendency exhibit survival curves with low “a/b” values
E. Split dose recovery is predicted by the “b” coefficient
Answer: D
Cells comprising tumors with pro-apoptotic tendencies are gnerally characterized with a high “a/b” value. ALWAYS think clnically about lymphoma with pro-apoptotic tumors; these have high a/b.
2020-G6. Concerning cell survival curves, which of the following statements is true?
A. Cells with survival curves characterized by large “a/b” ratios will generally exhibit a high level of sparing with dose fraction
B. The “a/b” value represents the surviving fraction at which the linear and quadratic contributions to cell killing are equal
C. The effective survival curve for a multi-fraction regimen is usually exponential
D. The initial linear component of the survival curve is due to the accumulation of sub lethal damages whereas the quadratic component is due to production of irreparable lethal damages.
E. Cells derived from the same type of normal tissue, but from different individuals, show large differences in radiosensitivity
Answer: C
The effective survival curve for a multi-fraction regimen generally follows an exponential response.
Cells that display survival curves with large “a/b” values tend to show relatively little sparing with fractionation since “a” inactivation will dominate.
The “a/b” ratio is the dose (not level of survival) at which the linear and quadratic contributions to cell killing are equal.
The initial killing is caused by the production of irreparable damage while the quadratic portion of the survival curve results from the accumulation of sub lethal damage.
The radiosensitivies of normal tissues from different individuals usually exhibit relatively little variation.
2020-G7. Adjuvant therapies that affect repair rates of “b” type injury:
A. Will have little effect on tissue sensitivity to radiation
B. Will substantially increase tissue sensitivity to radiation
C. Will substantially decrease tissue sensitivity to radiation
D. Is predicted to produce therapeutic gain by interfering with tumor tissue repair
E. None of the above
Answer: A
Adjuvant therapies (gene therapy, drugs, microencironmental manipulation) may affect repair rates of beta-type injury will have little effect on tissue sensitivity to radiation.
2020-G8. Radiation sensitization can be demonstrated in cell culture by:
A. an increase in the slope of the oxygenated cell survival curve
B. an increase in the slope of the hypoxic cell survival curve
C. reduction in mean inactivation dose, D0
D. removal of the shoulder of a cell survival curve
E. all of the above
Answer: E
Radiosensitization is observed as a leftward shift of cell survival curves which is described by all the above A-D
2020-G9. The shoulder in cell survival curves is most pronouced when cells are irradiation with:
A. 1 MeV neutrons
- 2 MeV alpha particles
C. 5 MeV electrons
D. 100 MeV pi mesons
E. 220 KVp X-rays
Answer: C
The shoulder of the survival curve (the “b” component) is most pronounced for low LET radiation and minimal for high LET radiations.
For a given particle the LET goes down as the energy goes up.
For a given energy, the LET increases with the mass of the particle.
Electrons are by far the lightest of the particles listed; pi mesons are the next lightest, then neutrons with alpha particles the heaviest.
NOTE: Photons cannot be described by LET. Remember that the definition of LET is the amount of energy that an ionizing particle transfers to the material traversed per unit distance.
2020-H1. A cell line is irradiated with 6 MeV X-rays under both aerobic and severely hypoxic conditions. The OER, defined from the slopes of the aerobic and hypoxic survival curves is found to be 3.2. Approximately what OER would you expect to see if the same cells were irradiated with 15 MeV neutrons using the same protocols?
A. 3.2
B. 2.8
C. 2.2
D. 1.6
E. 1.0
Answer: D
The OER decreases as LET increases, falling to 1.0 at very high LETs (alpha).
Neutrons are intermediate in ionization density and thus have intermediate LET calues and therefore an OER typically about 1.6.
2020-H2. The correct ranking of the following radiations in order of increasing LET is:
A. 50 keV X-rays, 20 MeV photons, 20 MeV alpha, 250 keV alpha
B. 20 MeV alpha, 250 keV alpha, 20 MeV photons, 50 keV x-rays
C. 250 keV alpha, 20 MeV alpha, 50 keV x-rays, 20 MeV photons
D. 20 MeV photons, 50 keV x-rays, 250 keV alpha, 20 MeV alpha
E. 20 MeV photons, 50 keV x-rays, 20 MeV alpha, 250 keV alpha
Answer: E
LET is proportional to the size and charge of a particle and inversely proportional to energy including the fast electrons created by interaction of photons with atoms and molecules
NOTE: In this explanation, the photon/x-ray “LET” infers to secondary electrons technically, not the photon itself
Remember that the lower energy for a given particle, the higher the LET
2020-H3. Fast neutrons become more widely accepted and were selected for use in experimental clinical radiotherapy:
A. to overcome hypoxic radioresistance
B. based on the premise that RBE values are smaller in slowly proliferating tumors
C. because of consistent pre-clinical observations that neutron appeared to have a clear advantage over x-rays or y-rays in most tumor types and locations
D. since they were easier to administer than photons
E. none of the above
Answer: A
The major rationale for neutron therapy was the reduced OER observed in cell and tissue radiobiology experiments that might improve therapeutic ratio
2020-H4. Which of the following statements concerning LET is false?
A. The highest RBE occurs for radiation with LET values of approximately 100 keV/um
B. High LET radiations yield survival curves with low D0 values
C. The OER increases with increasing LET
D. High LET radiations often produce exponential survival curves
E. LET is an average energy (in keV) transferred from a charged particle traversing a distance of 1 um in the medium
Answer: C
OER decreases with increasing LET.
Maximum effectiveness and therefore RBE reaches a peak for radiation whose LET is approximately 100 keV/um.
The RBE of high LET radiation is generally high resulting in low values for D0. The survival curves resulting from irradiation of cells with high LET radiations are typically exponential.
LET is the term that describes the density of ionizations or the aberage amount of energy lost (in keV) to the medium per unit of track length (um)
2020-H5. What is the effect on both RBE and the “a/b” ratio as the LET for the type of radiation increases up to 100 keV/um?
A. both remain the same
B. both increase
C. both decrease
D. the RBE decreases while the “a/b” decreases
E. the RBE increases while the “a/b” decreases
Answer: B
RBE and “a/b” ratio increase with LET
2020-H6. A cell line irradiated with x-rays under aerobic conditions is well fit by a survival curve for which n=3 and D0 = 1.5 Gy. Which of the following survival curve parameters would best apply under the irradiation and oxygenation conditions indicated?
A. X-rays at pO2 of 1 mm Hg; n=1 and D0=0.5 Gy
B. 14 MeV neutrons in air; n=10 and D0=3 Gy
C. X-rays at pO2 of 5 mm Hg; n=2 and D0=1.0 Gy
D. 2.5 MeV a-particles at pO2 of 1 mm Hg; n=1, D0=0.5 Gy
E. 200 MeV protons in air; n=1 and D0=0.3 Gy
Answer: D
The a-particles have a survival curve characterized by a small n and D0 even under hypoxic conditions. The D0 is expected to increase for x-rays under hypoxic conditions. High energy protons have similar biologic properties to x-rays.
NOTE: Remember that n is the extrapolation number which is the slope projected back to the Y axis, always at minimum of 1. The broader the shoulder before starting the slope (AKA the more sub lethal damage repair occuring), the higher the extrapolation number.
2020-H7. Concerning cellular radiation response and LET, which one of the following statements is true?
A. RBE reaches a maximum for radiations with LET values in the range of approximately 25 keV/um
B. High LET radiations tend to produce exponential survival curves
C. High LET radiations yield survival curves with higher D0 values than low LET radiations
D. Oxygen plays a greater role as a radiation sensitizer for high LET compared to low LET radiations
E. There is a greater variation in sensitivity through the cell cycle for high LET compared to low LET radiations
Answer: B
High LET radiations are generally characterized by exponential survival curves.
RBE reaches a peak around 100 keV per micron. High LET radiations generally exhibit higher RBEs than low LET radiations resulting in greater cellular sensiticity and lower D0 values.
Oxygen plays a diminished role in high LEt compared to low LET radiations as large numbers of lethal DNA damages are produced in cells indepedent of damage fixation by oxygen.
There is less cell cycle variation in sensiticity for high LET compared to low LET radiations.
2020-I5. The approximate partial pressure of oxygen at which y-irradiated cells exhibit a radiosensitivity halfway between their fully aerobic and fully hypoxic response is:
A. 0.1 mm Hg
B. 4 mm Hg
C. 30 mm Hg
D. 150 mm Hg
E. 760 mm Hg
Answer: B
Half maximal radiosensitization is usually observed at an oxygen pressure of roughly 3-5 mm Hg
2020-L2. Which of these strategies to address hypoxia are being explored?
A. Fractionation with high LET radiation
B. Hypoxic cell radiosensitizers
C. Small molecule inhibitors of HIF-1 activity
D. Use of bioreductive alkylating agents
E. Reversal of tumor hypoxia
Answer: C
2020-L6. Which of the following statements concerning tumor hypoxia is true?
A. Regions of chronic hypoxia may develop in tumors due to the temporary closing of a blood vessel
B. Chronically hypoxic regions in rodent tumors generally exhibit slow reoxygenation while acutely hypoxic regions display rapid reoxygenation
C. Even in the abscence of oxygenation, essentially all hypoxic cells will be elimated from a tumor following a typical course of radiotherapy
D. Generally as a tumor increases in size, the percentage of hypoxic cells decreases
E. It is rare to observe areas of chronic hypoxia in tumors until the distances between blood capillaries and tumor cells exceed 1 mm
Answer: A
Patients who have tumors with relatively low median pO2 levels and therefore hypoxic regions, tend to have more aggressive tumors and therefore exhibit lower levels of survival regardless of their treatment
NOTE: While technically temporary closing of a blood vessel is acute hypoxia, repeated episodes of this can lead to cyclic episodes of hyoxia that can cause chronic hypoxia.
Remember that hypoxia occurs >100 um, not 1 mm
2020-M1. CDK1/ Cyclin A is involved in the transition from:
A. G0 into G1
B. G1 into S
C. S into G2
D. G2 into M
E. M into G1
Answer: B
The CDK1/ Cyclin A complex is critical for transition of cells from G1 phase into S-phase.
NOTE:
G1 (G0) -> S -> G2 -> M
G1 -> S (Cyclin D + Cdk4/6), (Cyclin E + Cdk2)
S -> G2 (Cyclin A + Cdk2)
G2 -> M (Cyclin A/B + Cdk1)
2020-N1. PTEN inhibits which pathway:
A. VEGF
B. EGFR
C. p53
D. PI3K-Akt
E. KRAS
Answer: C
PTEN dephosphorylates the 3’ phosphate of the inositol ring in PIP3 resulting in the bi-phosphate product PIP2. This de-phosphrylation is important because it results in inhibition of the Akt signaling pathway.
2020-N7. Which statement regarding the Ras family of oncogenes is true?
A. RAS proteins are binary molecular switches that cycle between inactive guanosine triphosphate (GTP)-bound and active guanosine diphosphate (GDP) bound states
B. Loss of function of Ras bypass the normal growth regulatory signals of a cell by being locked in an “off” state
C. The Ras family includes H-Ras, K-Ras, and N-Ras
D. One major pathway directly regulated by Ras is the PI3K pathway which regulates cell growth through glucose signaling
E. There are no congenital syndromes linked to Ras germline mutations
Ras is a family of genes frequently found to harbor a mutation in human tumors. This family consists of 3 functional genes H-Ras, K-Ras, and N-Ras.
They are mutated in 20-25% of human tumors. Ras proteins are binary molecular switches that cycle between active guanosine triphosphate (GTP)-bound and inactive guanosine diphosphate (GDP) bound states.
Ras are oncogenes, their gain of function prevents the need for external signals from growth factors to activate them.
The Ras/PI3K/Akt/TOR (target of rapamycin) pathways has long been known to be important in regulating cell growth through insulin signaling.
Recent observations have brought to light the occurances of various germline ras mutations occuring in association with various hereditary familal developmental syndromes (RASopathies) such as neurofibromatosis type 1.
2020-Q9. After an acute whole body radiation dose within what range, is a bone marrow transplant likely to be an effective treatment?
A. doses 2-10 Gy
B. doses 2-4 Gy
C. doses 6-8 Gy
D. doses 8-10 Gy
E. doses 10-50 Gy
Answer: D
Bone marrow transplantation is likely to only be a reasonable response after acute total body irradiation in the range from 8-10 Gy. With lower dosese, survival is likely with appropriate supportive care.
With higher doses, survival is unlikely and death is usually the result of failure of the GI system.
2020-T4. What parameter defines the slope of a tumor control probability curve?
A. alpha
B. beta
C. alpha/beta
D. y (gamma)
E. u (mu)
Answer: D
When tumor control rates lie between 10-85%, a useful practical description of the slope of the tumor control probability (TCP) curves is the percentage point change in TCP for a 1% change in tumor dose, the y-value.
The y-value is determined by clonogenic radiosensitivity, the curve being steeper the more sensitive the tumor cells.
2020-T5. The increase in tumor control probability with dose for clinically detectable tumors is theorectically best described by which of the following:
A. A log-linear curve
B. A sigmoid curve with a dose threshold
C. A sigmoid curve with no threshold
D. A curve that is closer to linear with no threshold
E. A linear with a dose threshold
Answer: B
Certain level of dose threshold is required in order to observe cure. After that it will be determined by the killing of the last surviving clonogens, which will be a sigmoid curve.
2020-U3. If a tumor has a potential doubling time of 3 days, the treatment regimen most likely to be effective at controlling it is:
A. hyper-fractionation
B. accelerated treatment
C. split course
D. conventional treatment
D. hypofractionation
Answer: B
Accelerated fractionation may be indicated for rapidly proliferating tumors
NOTE: Remember that RTOG 9003 was a Stage 3/4 H&N SCC trial comparing 4 different dose regimens:
- Standard: 70 Gy/35 daily fractions/7 weeks
- Hyperfractionated: 81.6 Gy/68 BID fractions/ 7 weeks
- Accelerated-Split course: 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy
- Accelerated-Continuous: 72 Gy/42 fractions/6 weeks.
The 3 experimental arms were to be compared with standard FX. At 5 years, only hyperfractionation improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.
