1) Which of the following statements is TRUE concerning chromosomal aberrations in cells after whole body X-irradiation?
A. The formation of terminal deletions follows an exponential dose response.
B. Translocations are an unstable type of chromosome aberration.
C. The number of dicentric chromosomes detected in peripheral blood lymphocytes remains relatively constant with time.
D. SKY (spectral karyotyping) is a useful method for detection of stable aberrations decades following irradiation.
E. The minimum dose that can be estimated by scoring dicentric chromosomes is 2 Gy.
2) Which of the following types of chromosome aberrations is most responsible for the formation of micronuclei observed after irradiation?
A. sister chromatid exchanges
B. chromatid gaps
C. inversions
D. quadriradials
E. acentric fragments
3) Telomere shortening in primary human fibroblasts ultimately results in:
A. chromosomal fusion
B. cell necrosis
C. replicative cell senescence
D. genomic instability
E. neoplastic transformation
4) Which of the following is the best measure for the presence of radiation-induced chromosome aberrations in interphase cells?
A. reciprocal translocations
B. ring chromosomes
C. dicentric chromosomes
D. micronuclei
E. chromatid breaks
5) Which one of the following statements concerning the induction of chromosome aberrations is INCORRECT?
A. Primary radiation-induced breaks can reconstitute without apparent morphological change to the chromosome, rejoin illegitimately with another break site to produce an intra- or inter-chromosomal aberration, or remain “open,” leading to a simple break.
B. There is compelling evidence that the induction and interaction of DNA double-strand breaks is the principal mechanism for the production of chromosome aberrations.
C. Dicentrics, centric rings, and translocations are formed following X-irradiation of cells in the G0/G1 phase of the cell cycle, and follow a linear-quadratic dose response.
D. Fluorescence in situ hybridization (FISH) using multi-colored probes has allowed chromosome aberration complexity to be studied in detail.
E. Chromatid type aberrations are observed when cells are irradiated during the G1 phase of the cell cycle.
6) The formation of dicentric chromosome aberrations follows a linear-quadratic dose response curve. This has been interpreted to mean that the production of dicentric chromosomes results from:
A. two chromosome breaks, produced either by one or by two separate radiation tracks
B. two chromosome breaks produced by two separate radiation tracks
C. two chromosome breaks produced by a single radiation track
D. one chromosome break produced by two separate radiation tracks
E. one chromosome break produced by a single track of radiation
7) Which of the following statements is TRUE concerning chromosomal aberrations?
A. A ring chromosome is an example of a chromatid-type aberration.
B. A dicentric is a stable chromosome aberration.
C. Breakage of a single chromatid in G2 often leads to the formation of an anaphase bridge.
D. Terminal deletions are induced as a linear function of dose.
E. For low LET radiation, the yield of dicentric chromosomes is inversely proportional to the dose-rate.
8) Increased numbers of chromosome aberrations, especially quadriradials, are frequently found even in the absence of radiation, in which of the following human syndromes?
A. Ataxia telangiectasia
B. Fanconi anemia
C. Cockayne’s syndrome
D. Niemann-Pick disease
E. SCID
9) Pathways that trigger apoptosis culminate in widespread intracellular proteolysis. Which of the following proteases is a downstream executioner that directly participates in the breakdown of numerous cellular proteins?
A. caspase-8 (CASP3)
B. caspase-9 (CASP9)
C. caspase-3 (CASP3)
D. caspase-10 (CASP10)
E. XIAP (BIRC4)
10) Which of the following statements regarding cell death following radiotherapy is CORRECT?
A. The majority of solid epithelial tumors regress during treatment because of radiation-induced apoptosis.
B. The intrinsic apoptotic pathway can be triggered either by radiation-induced DNA damage or by sphingomyelin-mediated damage to the outer plasma membrane.
C. A novel drug that abolishes the G1 checkpoint would be expected to reduce the incidence of mitotic catastrophe in irradiated cells.
D. Cells that undergo replicative senescence following radiotherapy are characterized by increased membrane blebbing and DNA fragmentation.
E. The presence of γ-H2AX histone foci in irradiated cells is indicative of sphingomyelin activation.
11) Which of the following delayed effects has NOT been observed in bystander cells following exposure to ionizing radiation?
A. persistent reduction in plating efficiency
B. presence of chromosome aberrations
C. presence of DNA damage
D. decrease in the concentration of reactive oxygen species
E. induction of neoplastic transformation
12) Radiation-induced cellular senescence can contribute to long-term organ dysfunction by:
A. inducing mitotic catastrophe
B. depleting clonogenic stem cells
C. increasing oxidative stress secondary to mitochondrial dysfunction
D. causing permanent G2 arrest
E. limiting nutrient supply to the organ
13) The extrinsic pathway of apoptotic cell death requires:
A. signals derived from changes in chromatin conformation
B. activation of death receptors that translocate from the plasma membrane to the nucleus and degrade DNA
C. engagement of death receptors located on the plasma membrane that lead to activation of the initiator caspase-8 (CASP8)
D. p53 (TP53) activation
E. the triggering of changes in mitochondrial membrane potential
14) One hallmark of the apoptotic process is the display of phosphatidylserine residues on the outer surface of the plasma membrane. This is an important event in terms of the tissue response to ionizing radiation because it:
A. helps recruit death ligands expressed by neighboring cells to receptors on the cell surface
B. stimulates an inflammatory response to remove dying cells from the tissue
C. signals the recruitment of phagocytes that engulf the dying cells without causing an inflammatory response
D. is required for DNA condensation and fragmentation
15) Following irradiation, p53 (TP53) is involved in triggering apoptosis by:
A. mediating a transcriptional response that leads to accumulation of the proteins PUMA (BBC3) and BIM
B. stimulating the transcription of p21 (CDKN1A)
C. decreasing the expression of the multi-domain protein BAX
D. initiating the processing of the zymogen pro-caspase 9 to the active form, caspase-9 (CASP9) 20
E. triggering the transcription of GADD45A
16) Regarding the regulation of apoptosis, which of the following pairs of mammalian proteins and their apoptosis-related function is INCORRECT?
A. p53 (TP53) --- upregulation of BAX
B. DIABLO --- caspase activation
C. XIAP (BIRC4) --- caspase inhibition
D. BAX --- cytochrome c release
E. caspase-3 (CASP3) --- initiator caspase
17) Which ONE of the following is a morphological or biochemical feature of apoptosis?
A. random cleavage of DNA
B. cellular swelling
C. lack of dependence on ATP as an energy source
D. condensation of chromatin at the periphery of the nucleus
E. rupture of the plasma membrane
18) Mitotic catastrophe following irradiation:
A. is caused by an aberrant mitosis
B. follows from arrest of cells in the G1 phase of the cell cycle
C. is ATP dependent
D. is a result of radiation-induced senescence
E. occurs during interphase
19) The TUNEL assay used to identify apoptotic cells detects:
A. the action of BAX on the mitochondria
B. membrane integrity
C. mitochondrial release of cytochrome c
D. binding of TNFα (TNF) to its receptor
E. DNA fragmentation
20) Which of the following best describes the role of p53 (TP53) in the regulation of apoptosis? p53:
A. binds directly to sites of strand breaks in DNA
B. binds to death receptors on the cell membrane, thereby activating the extrinsic apoptotic pathway
C. activates BAX and BAK in the cytoplasm to control mitochondrial membrane permeabilization
D. inactivates procaspase-9
E. activates caspase-8
21) Which of the following best describes the radiation-induced bystander effect?
A. Damage to unirradiated normal tissue noted after irradiation of a tumor.
B. Cell killing that results from irradiation of the cell’s cytoplasm in the absence of direct irradiation of the nucleus.
C. Radiation-induced increase in cell membrane permeability that causes increased sensitivity to cytotoxic drugs.
D. DNA and chromosomal damage that occurs in unirradiated cells that are proximate to irradiated cells.
E. Intercellular communication that modifies the shoulder region of the radiation survival curve.
22) Which of the following in vivo assays of radiation response does NOT depend on a functional endpoint?
A. LD50
B. skin nodule formation
C. myelopathy
D. breathing rate
E. cognitive impairment
23) Using the linear-quadratic survival curve equation, what would the cell surviving fraction be following a dose of 2 Gy delivered acutely
(use α=0.3 Gy-1 and β=0.1 Gy-2)?
A. 0.01
B. 0.10
C. 0.37
D. 0.50
E. 0.90
24) For the same values of α and β used in the previous problem, what would be the approximate surviving fraction if the 2 Gy dose was delivered at a low dose rate over a 6 hour period instead of acutely (assume no repopulation takes place during the irradiation)?
A. 0.1
B. 0.2
C. 0.3
D. 0.5
E. 0.9
25) Which clonogenic assay has been used to measure the radiation sensitivity of bone marrow stem cells in vivo?
A. fat pad assay
B. lung colony assay
C. endpoint dilution assay
D. in vivo/in vitro excision assay
E. spleen colony assay
