1) Which of the following pairs of CDKs or cyclins is associated with the correct phase transition?
A. CDK1 (CDC2) – G2 into M
B. CDK4 – S into G2
C. cyclin A – G2 into M
D. cyclin B – S into G2
E. cyclin D – M into G1
2) Irradiation of an exponentially-growing population of cells in culture with a dose equal to the D10 tends to synchronize the surviving cells (initially) in which phase of the cell cycle?
A. G0
B. G1
C. S
D. G2
E. M
3) The typical cell cycle time (TC) for proliferating cells in human tumors is in the range of:
A. <1 day
B. 1-5 days
C. 6-25 days
D. 26-100 days
E. >100 days
4) Which of the following statements is TRUE concerning tumor growth kinetic parameters?
A. Often, the cell loss factor (φ) decreases several weeks after the start of radiotherapy.
B. The growth fraction (GF) is the ratio of the number of viable cells to the sum of viable and non-viable cells.
C. If the volume doubling time (TD) is 60 days and the potential doubling time (Tpot) is 3 days, then the cell loss factor is 5%.
D. Tpot has proven useful in predicting tumor response to accelerated radiotherapy.
E. Typically, the cell loss factor, φ, is of minor importance in determining a tumor’s volume doubling time.
5) Eponentially growing cells are pulse-labeled with tritiated thymidine and sampled as a function of time thereafter.The time required for the percent of labeled mitoses to reach 50% of its maximum value corresponds to approximately:
A. TS
B. TC
C. TG2
D. TG1 + TS/2
E. TG2 + TM/2
6) If the mitotic index of a cell line is 5%, the growth fraction is 100%, the cell cycle time is 14 hours and the correction factor, λ, is 0.7, how long is mitosis?
A. 0.2 hours
B. 1 hour
C. 2 hours
D. 4 hours
E. 8 hours
7) Which of the following is the main reason why the volume doubling time of a tumor rarely equals its potential doubling time?
A. high cell loss factor
B. high metastatic propensity
C. long cell cycle time
D. low hypoxic fraction
E. low growth fraction
8) Which of the following statements concerning tumor kinetics is TRUE?
A. Cell-cycle times (Tc) are longer than potential doubling times (Tpot) because of the presence of non-proliferating cells.
B. The Tpot is usually shorter than the volume doubling time because the growth fraction (GF) is usually less than 100%.
C. Tpot can be determined if the mitotic index (MI) and the duration of S phase (Ts) are known.
D. Tumors with long values for Tpot are good candidates for accelerated radiotherapy.
E. In the absence of cell loss, Tpot would equal the volume doubling time (TD) of the tumor.
9) Which of the following substrates and target sites of the ATM kinase are implicated in the control of the G2-checkpoint in X-irradiated cells?
A. CHK2 (CHEK2) and MDM2
B. NBS1 (NBN) and CHK2
C. CHK2 and CDC25C
D. CHK2 and p53 (TP53)
10) Which of the following pairs of chemicals would be used for analysis of cells in S phase and for an estimate of relative DNA content by flow cytometry?
A. bromodeoxyuridine and propidium iodide
B. tritiated thymidine and hydroxyurea
C. dichlorohydrofluorescein and cytochrome c
D. H2AX and ethidium bromide
E. sphingomyelin and ceramide
11) If a tumor was comprised of cells characterized by a high growth fraction and a short cell cycle time, which of the following would most likely describe the behavior of the tumor prior to and after treatement with a curative dose of radaition?
A. slow growth, slow regression
B. slow growth, rapid regression
C. rapid growth, rapid regression
D. rapid growth, slow regression
12) Following exposure of cells to 3 Gy from a 6 MV X-ray beam, the ATM protein is activated and phosphorylates multiple intracellular targets. Which of the following is NOT a target for ATM phosphorylation?
A. histone H2AX
B. p53 (TP53)
C. VEGF (VEGFA)
D. BRCA1
E. Artemis
13) Which of the following pairs of molecular events and their functional consequences is INCORRECT?
A. VHL inactivation ---- angiogenesis
B. cyclin D1 repression --- inhibition of proliferation
C. cytochrome c release --- apoptosis
D. ATM phosphorylation ---- epistasis
E. miRNAs mis-expression --- carcinogenesis
14) Which of the following pairs of transcription factors and genes they regulate is INCORRECT?
A. HIF-1 and VEGF (VEGFA)
B. NF-κΒ and IL-6
C. p53 (TP53) and p21(CDKN1A)
D. FOS and BRCA2
E. E2F and CDC25A
15) Which of the following statements concerning cytokines is CORRECT?
A. NF-κB is the critical cytokine responsible for the development of lung fibrosis following irradiation.
B. A paracrine response is the result of a cytokine targeting the same cell that produced the cytokine.
C. Most cytokines are tyrosine kinases.
D. Cytokines are proteins released by irradiated cells that stimulate tissues to produce a biological response.
E. An autocrine response is the result of a cytokine targeting cells adjacent to the cell that produced the cytokine.
16) Which of the following statements concerning the response of NF-κB to ionizing radiation exposure is FALSE?
A. NF-κB is a transcription factor.
B. The inhibitor of κB (IκB) is phosphorylated by ATM and degraded, allowing NF-κB to move from the cytoplasm into the nucleus.
C. NF-κB generally acts to stimulate apoptosis and enhance the radiosensitivity of cells.
D. Both DNA double-strand breaks and reactive oxygen species generated by radiation exposure can activate NF-κB.
E. NF-κB is sequestered as an inactive form in the cytoplasm by interaction with an inhibitory subunit of the IκB.
17) Based on functional genomic studies using microarray profiling, which one of the following statements best describes the transcriptional response of irradiated cells and tissues?
A. Many genes are up-regulated by radiation exposure, but down-regulation of genes is rarely observed.
B. The transcriptional response to radiation is complex, but for a given cell line, similar responses will be seen between 2 and 24 hours post-irradiation.
C. The transcriptional response is dynamic, varying with time after irradiation, but overall is similar for most cell lines examined to date.
D. Transcriptional responses depend on the time elapsed after irradiation, and on the cell’s tissue of origin, but do not vary significantly between cell types derived from the same tissue, or between different individuals.
E. Variability observed in transcriptional profiles between individuals may provide a basis for individualized medicine, allowing prediction of therapeutic responses.
18) Concerning the p21 (CDKN1A) protein, which of the following statements is TRUE?
A. Its transcription is transactivated by p53 (TP53) in response to ionizing radiation exposure.
B. It is required for entry into S phase of the cell cycle.
C. It is up-regulated only in cells exposed to radiation doses greater than 1 Gy.
D. Overexpression of p21 causes arrest in the G2 phase of the cell cycle.
E. It binds to BCL-xL (BCL2L1) to promote apoptosis.
19) Which of the following is NOT a mechanism for p53 (TP53) post-transcription modification following irradiation?
A. phosphorylation by CHK1 (CHEK1) and CHK2 (CHEK2)
B. phosphorylation by ATM and ATR
C. ubiquitination by MDM2
D. acetylation by p300/CBP
20) Which of the following statements is TRUE concerning the retinoblastoma protein (RB1)? RB1:
A. is the most important downstream effector controlling the G2 checkpoint
B. once phosphorylated, releases E2F
C. is encoded by an oncogene
D. is phosphorylated primarily by CDK1 (CDC2)
E. is inactivated in approximately 10% of cancers
21) Which statement is TRUE concerning the role of p53 (TP53) and p21 (CDKN1A) in the response of the cells to radiation?
A. p21 phosphorylates NBS1 (NBN), thereby stimulating homologous recombinational repair of DNA double-strand breaks.
B. p53-mediated G1 phase arrest results from the inactivation of p21.
C. A decrease in the amount of p53 can trigger apoptosis or G1 arrest.
D. p21 inhibits CDK-cyclin activity thereby decreasing phosphorylation of RB1.
E. DNA damage initiates a signal transduction pathway that results in a marked increase in transcription of the p53 gene.
22) Which statement is CORRECT concerning the ataxia telangiectasia-mutated (ATM) gene and protein?
A. Irradiated cells derived from a person diagnosed with ataxia telangiectasia (AT) exhibit normal S and G2 checkpoints, but an abnormal G1 checkpoint.
B. The ATM protein contains a domain resembling a phosphatidylinositol-3-kinase (PI3K).
C. An individual possessing one defective copy of the ATM gene will likely display symptoms of AT.
D. Cells derived from patients with AT typically display increased levels of p53 (TP53) phosphorylation.
E. Irradiation causes autophosphorylation of ATM which converts it from an active monomer to an inactive dimer.
23) Which of the following pairs of cancer type and corresponding common genetic alteration in that cancer is INCORRECT?
A. pancreatic --- K-RAS
B. kidney --- VHL
C. lung ---- PTCH
D. thyroid ---- RET
24) Which of the following pairs of tumor suppressor proteins and their corresponding functions is INCORRECT?
A. APC — signal transduction
B. RB1 — cell cycle regulation
C. p53 (TP53) — cell cycle and apoptosis regulation
D. WT1 — translational regulation
E. BRCA1 — DNA damage repair
25) A possible advantage of cytosine deaminase gene therapy combined with radiotherapy is:
A. the non-viral nature of the vectors used for its delivery
B. its ability to activate gancyclovir to a toxic product
C. the limited bystander effect observed with this agent
D. its ability to cause radiosensitization when administered either before or after irradiation
E. that the deaminated product is freely diffusible
26) Which of the following statements is TRUE concerning p53 (TP53)? p53:
A. is encoded by an oncogene that is activated in the majority of human cancers
B. is inactivated in the presence of DNA damage
C. inhibits expression of the GADD45A, p21 (CDKN1A) and PCNA genes
D. can be inactivated by Epstein-Barr virus (EBV)
E. is modified by either phosphorylation or acetylation in response to DNA damage
27) Which of the following classes of genes are considered “caretakers”?
A. oncogenes
B. proto-oncogenes
C. cyclin genes
D. DNA repair genes
E. signal transduction genes
28) Oncogenes were first discovered from the study of:
A. retroviruses
B. bacteria
C. yeast
D. mice
E. human cells in culture
29) Which of the following pairs of genes or portions of genes and corresponding descriptors is CORRECT?
A. tumor suppressor genes – activated in many human tumors
B. exon – the non-coding region of a gene
C. promoter – involved in gene regulation
D. DNA repair gene – EGFR
E. oncogene – activated through loss of heterozygosity
30) Which one of the following is NOT a tumor suppressor gene?
A. PTEN
B. BRCA2
C. WT1
D. NF1
E. ABL
31) The most consistently observed effect on the radiation response of tumor cells possessing a mutation in the p53 (TP53) gene is:
A. increased radioresistance
B. prolonged G2 arrest
C. increased DNA repair
D. loss of G1/S checkpoint
E. lengthening of mitosis
