Rabex 2005 G, H, I, J, K, L, M, N

Front 1

G1) In the linear-quadratic survival curve model, lnSF = -αD-βD2, α 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 β when the α/β ratio is fixed.

E. equal to the reciprocal of SF2 .

Back 1

G1) C

α defines the initial slope of the survival curve.

Front 2

G2) The cells that would be expected to have the smallest X-ray D0 would be:

A. fibroblasts from a normal volunteer.

B. fibroblasts from a radiation-exposed person.

C. fibroblasts from a person diagnosed with ataxia telangiectasia.

D. fibroblasts from a patient with xeroderma pigmentosum.

E. lymphocytes from a normal volunteer.

Back 2

C

Although lymphocytes are radiosensitive, fibroblasts from a homozygous A-T patient would be the most radiosensitive. XP patients are sensitive to UV, not ionizing radiation.

Front 3

G3) For cells in mitosis at the time of irradiation, the cell survival response is best described by which of the following models?

A. Single-hit/single-target

B. Multi-hit/single-target

C. Single-hit/multi-target

D. Single-hit/single-target combined with single-hit/multi-target

E. None of the above

Back 3

A

Cells in the M phase typically exhibit no shoulder on their cell survival curves. Hence the simple exponential target theory model (single-hit/single-target) is appropriate.

Front 4

G4) Approximately how many cells will survive in a tumor containing 10^9 clonogens after a fractionated treatment to a total dose of 40 Gy, assuming the effective D10 is 5 Gy?

A. 0

B. 10^1

C. 10^2

D. 10^5

E. 10^8

Back 4

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 the tumor initially contained 10^9 clonogenic cells, it is anticipated that 10^1 cells will survive.

Front 5

G5) The TD5/5 for a certain tissue irradiated with 2 Gy fractions is 60 Gy, whereas for 4 Gy fractions it is 40 Gy. Assuming that the linear quadratic equation accurately predicts the dose response for this tissue, what is the value of α/β?

A. 1 Gy

B. 2 Gy

C. 4 Gy

D. 10 Gy

E. 20 Gy

Back 5

B

For the TD5/5 values to be equal for the two fractionation regimens, the BED values for the two treatment must be equal. Therefore, using the equation BED = nd[1+(d/α/β)], where n is the number of fractions, d is the dose per fraction and α/β is a tissue specific parameter, 60[1+(2/α/β)] = 40[1+(4/α/β)] and thus α/β = 2 Gy.

Front 6

G6) The β coefficient of the linear-quadratic model:

A. is a measure of non-reparable damage.

B. tends towards zero for low-LET irradiation of mammalian cells.

C. correlates positively with the LET of the radiation.

D. decreases with further fractionation/protraction of the total dose.

E. has units of Gy-1.

Back 6

D

β is an indicator of the extent of cell killing due to the accumulation of sublethal damage. As the time over which a dose of radiation is delivered increases, there is more opportunity for the repair of sublethal damage, and hence β decreases.

Front 7

G7) The α/β ratio in the linear-quadratic model is:

A. the dose where the value of α equals the value of β.

B. small for cells or tissues having relatively little repair capability.

C. an indicator of the fractionation sensitivity of cells or tissues.

D. unusually large for the induction of skin fibrosis.

E. typically smaller for early responding tissues than late responding tissues.

Back 7

G7) C

The α/β ratio is a reflection of the sensitivity of cells and tissues to fractionation. It is also the dose at which the cell killing caused by the αD component is equal to the killing caused by the βD2 component. It is large for cells that exhibit relatively little sparing with fractionation. It is low for the late response of skin fibrosis and tends to be larger for early reacting tissues compared with late responses

Front 8

G8) 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 α value.

B. Fitting survival data to the single-hit, multi-target equation usually underestimates cell killing at low doses.

C. Differences in the intrinsic radiosensitivities of tumor cells are expressed mainly as differences in the α coefficient.

D. Tumors with a pro-apoptotic tendency exhibit survival curves with low α/β values.

E. Split dose recovery is predicted by the β coefficient.

Back 8

G8) D

Cells comprising tumors with pro-apoptotic tendencies are generally characterized with a high α/β value.

Front 9

G9) Concerning cell survival curves, which of the following statements is TRUE?

A. Cells with survival curves characterized by large α/β ratios will generally exhibit a high level of sparing with dose fractionation.

B. The α/β 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 sublethal damages whereas the quadratic component is due to the production of irreparable lethal damages.

E. Cells derived from the same type of normal tissue, but

Back 9

G9) C The effective survival curve for a multi-fraction regimen generally follows an exponential response. Cells that display survival curves with large α/β values tend to show relatively little sparing with fractionation since α-inactivation will dominate. The α/β 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 sublethal damage. The radiosensitivities of normal tissues from different individuals usually exhibit relatively little variation.

Front 10

G10) If α = 0.3 Gy-1 and β = 0.1 Gy-2, the percentage of cells surviving a single dose of 2 Gy is:

A. 0.25%

B. 2.7%

C. 10%

D. 23%

E. 37%

Back 10

G10) E Percent SF = (100%) exp(-αD - βD2) = (100%) exp[(-0.3 x 2) – (0.1 x 4)] (100) = (100%) e-1 = 37%

Front 11

G11) In a cell survival experiment with Chinese hamster cells cultured in vitro, 100 unirradiated cells were seeded and allowed to grow for seven days before colonies were fixed and stained for counting. 80 colonies were counted. In a second group, 1000 cells that had been irradiated to a dose of 5 Gy were seeded and 40 colonies counted. The cell surviving fraction (SF) after 5 Gy was:

A. 0.8

B. 0.5

C. 0.4

D. 0.05

E. 0.04

Back 11

G11) D

100 unirradiated cells yielded 80 colonies. Therefore, the plating efficiency of the cells is 0.8. Thus, the surviving fraction following 5 Gy is 40/(1000)(.8) = 0.05.

Front 12

H1) The correct ranking of the following radiations in order of increasing LET is:

A. 50 KeV X-ray, 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.

Back 12

H1) 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.

Front 13

G12) A whole body dose of 7 Gy of γ-rays would produce severe, potentially lethal hematologic toxicity. Assuming that the D0 of hematopoietic stem cells is 1 Gy and that these cells have a negligible capacity to repair sublethal damage, the surviving fraction after this 7 Gy radiation dose would be approximately;

A. 10-7

B. 10-6

C. 10-5

D. 10-4

E. 10-3

Back 13

G12) E

The D10 = 2.3 x D0 for an exponential survival curve. Therefore, the D10 for these cells is 2.3 x 1 Gy = 2.3 Gy. Therefore, an exposure to 7 Gy will result in a surviving fraction approximately of 10-^3

Front 14

H2) Each of the following statements concerning radiobiological parameters is correct, except:

A. LET is typically in units of keV/μm.

B. Heavy-charged particles are characterized by RBE values greater than 1.0.

C. The OER for single X-ray doses is generally in the range of 2-3.

D. The SER is the ratio of doses required to produce an equal biological effect in cells or tissues irradiated in absence and presence of a sensitizing agent, respectively.

E. For hyperthermia, the TER usually decreases with increasing temperature.

Back 14

H2) E

The thermal enhancement ratio (TER), which is the radiation dose to produce a particular effect in the absence of heat divided by the dose to produce the effect when heat is used, generally increases with the temperature.

Front 15

H3) 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/μm

B. High-LET radiations tend to produce exponential survival curves

C. High-LET radiations yield survival curves with higher Do values than low-LET radiations

D. Oxygen plays a greater role as a radiation sensitizer for high-LET compared with low LET radiation.

E. There is a greater variation in sensitivity through the cell cycle for high-LET compared with low-LET radiations

Back 15

H3) 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 sensitivity and lower D0 values. Oxygen plays a diminished role in high-LET compared with low-LET radiations as large numbers of lethal DNA damages are produced in cells independent of damage fixation by oxygen. There is less cell cycle variation in sensitivity for high-LET compared with low-LET radiations

Front 16

I1) The approximate partial pressure of oxygen at which γ-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

Back 16

I1) B

Half-maximal radiosensitization is usually observed at an oxygen pressure of roughly 3-5 mm Hg.

Front 17

I2) Cells reach full radiosensitization at a partial oxygen pressure of approximately:

A. 1 mm Hg

B. 5 mm Hg

C. 40 mm Hg

D. 150 mm Hg

E. 750 mm Hg

Back 17

I2) C

The radiosensitivity of mammalian cells changes very little at O2 tensions above those found in venous blood (20-40 mm Hg).

Front 18

I3) Concerning the role for oxygen in the radiation response, which of the following statements is TRUE?

A. In order to observe full radiosensitization, oxygen may be added to a hypoxic system up to 10 minutes after irradiation.

B. Radiosensitization is usually only observed for oxygen concentrations exceeding those found in venous blood.

C. An X-ray dose must be increased approximately 3-fold to achieve the same level of cell killing in hypoxic compared to aerated cells.

D. Oxygen plays a greater role in the sensitization of cells to high-LET radiation compared with low-LET radiation.

E. The hypoxic fraction in rodent tumors tends to remain constant for several months post-irradiation.

Back 18

I3) C

For single doses, the x-ray OER is usually about 3. Oxygen must be present during or within milliseconds of irradiation to observe full radiosensitization. Radiosensitization is observed at oxygen pressures lower than that typical of venous blood. Oxygen plays a diminished role in cells exposed to high LET compared with low LET radiations. As a result of reoxygenation, hypoxic cells usually become aerated within hours or days following an x-ray treatment.

Front 19

I4) At an O2 concentration of 50 mmHg, the D0 for a population of cells is 1.5 Gy, whereas the D0 at an O2 pressure of 250 mm Hg would be approximately:

A. 0.5 Gy

B. 0.75 Gy

C. 1.5 Gy

D. 3.0 Gy

E. 4.5 Gy

Back 19

I4) C

The radiosensitizing effect of O2 plateaus at a maximum value at about 20-40 mm Hg.

Front 20

I5) The oxygen enhancement ratio (OER):

A. is in the range of 4-8 for most cell lines in vitro irradiated with large, single doses.

B. shows a strong dose dependency at doses greater than about 3 Gy.

C. is typically greater for high-LET radiations compared to X-rays.

D. increases as the oxygen tension decreases from 80 to 5 mm Hg.

E. is lower for types of radiation predisposed to killing cells by a single-hit mechanism.

Back 20

I5) E

Oxygen plays a lesser role in enhancing cell killing for radiations that are characterized by exponential survival curves, such as high LET radiations. The x-ray OER is usually about 2-3 following single doses, , it does not show a dose dependency for relatively high doses, is usually smaller for high LET compared with low LET radiation and increases as the oxygen pressure decreases

Front 21

I6) 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 α-particles at pO2 of 1 mm Hg; n = 1 and D0 = 0.5 Gy

E. 200 MeV protons in air; n = 1 and D0 = 0.3 Gy

Back 21

I6) D

α-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.

Front 22

I7) 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

Back 22

I7) D

The OER decreases as the LET increases, falling to 1.0 at very high LETs. Neutrons are intermediate in ionization density and thus have intermediate LET values and therefore an OER typically about 1.6.

Front 23

JI) Concerning dose rate effect, which one of the following statements is TRUE?

A. Increasing the X-ray dose rate from 3 to 10 Gy/min results in little or no increase in the effectiveness for a given total dose.

B. Killing of bone marrow stem cells generally shows a large dose rate effect.

C. High-LET radiations are associated with significant dose rate effects.

D. Dose-rate has no effect on the yield of chromosome aberrations in X-irradiated cells.

E. Reduced cell killing with a decreasing dose rate is referred to as the "inverse dose rate effect".

Back 23

J1) A

Other than extremely high dose rates, increasing the dose rate above 1 Gy/min would have relatively little effect upon the effectiveness of the radiation since there would be little or no repair during the irradiation. Bone marrow stem cell killing and high LET radiations show relatively little effect of dose rate. The chromosome aberration yield is affected by dose rate. When decreasing the dose rate results in an increased level of cell killing, it is referred to as the inverse dose rate effect.

Front 24

J2) Sublethal radiation damage repair (SLDR):

A. occurs preferentially in malignant tissues.

B. plays a greater role in the recovery of tissues exposed to high-LET compared with low-LET radiations.

C. occurs only during high dose rate irradiations.

D. is demonstrated using split dose experiments.

E. is usually stimulated by hyperthermia.

Back 24

J2) D

Exposure to an X-ray dose in two fractions, rather than a single dose, results in a higher level of survival due to repair of sublethal damage between the fractions. Repair of sublethal damage takes place in both normal and malignant cells. The killing of cells by high-LET radiations involves a greater proportion of irreparable damages, rather than the accumulation of sublethal lesions that are reparable. Very little SLDR occurs during a high dose rate irradiation. Hyperthermia can inhibit repair of sublethal damage.

Front 25

J3) The inverse dose-rate effect is due to:

A. repair of sublethal damage.

B. accumulation of cells in the G2 phase of the cell cycle.

C. radiation-induced cell proliferation.

D. repair of potentially lethal damage.

E. oxygen radiosensitization.

Back 25

J3) B

The inverse dose rate effect is due to the accumulation of cells in the radiosensitive G2 phase of the cell cycle.

Front 26

J4) PLDR:

A. occurs in normal tissues, but not in tumors.

B. is that component of damage that can be altered by the conditions after irradiation.

C. is not affected by hypoxia, pH or availability of nutrients.

D. usually affects only the shoulder of the cell survival curve.

E. decreases in multifraction regimens compared to single fractions.

Back 26

J4) B

By definition, PLDR is that component of damage that can be altered by the conditions to which cells are exposed after irradiation. It appears to occur in both tumors and normal tissues, it is decreased in severe hypoxia or when nutrients are depleted, it increases at low pH and it usually affects the slope of cell survival curves, not the shoulder. Effect of fractionation on PLDR has not been carefully documented, but if anything it may be expected to increase with fractionation.

Front 27

K1) Human tumor cells grown as xenografts in SCID mice are frequently used as models in experimental cancer therapy. SCID mice can be used as hosts for human tumors because:

A. they have been engrafted with human bone marrow.

B. they have a developmental abnormality that prevents maturation of the thymus.

C. they have a DNA repair defect that leads to immune deficiency.

D. their immune systems have been ablated by whole body irradiation.

E. the human tumors are implanted into the renal capsule, an immune-privileged site.

Back 27

K1) C

SCID mice have a mutation which causes deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. This also leads to a deficiency in production of immunoglobulins and immunodeficiency.

Front 28

L1) All of the following statements concerning hypoxia are true, except:

A. Hypoxia induces apoptosis in cells having wild-type p53.

B. Hypoxia can generally be detected in tumor cells beyond more than approximately 10 μm from a functioning capillary.

C. Hypoxic conditions may select for tumor cells bearing mutant p53.

D. Hypoxia decreases radiosensitivity more for low-LET radiation than for high-LET radiation.

E. Tumors containing hypoxic regions display biphasic single-dose, X-ray survival curves.

Back 28

L1) B

Hypoxic regions can be detected at roughly 70 μm from a blood capillary. Hypoxia causes cells with wild-type p53 to apoptose, followed by the selective proliferation of cells with mutant p53, which do not apoptose. Hypoxic cells are relatively resistant to low-LET radiation, with an OER of ~3, but for some radiations of high-LET the OER is close to 1.0. A biphasic survival curve is observed for a population containing hypoxic cells due to their relative radioresistance.

Front 29

L2) The percentage of clonogenic tumor cells that are radiobiologically hypoxic in animal tumors averages approximately:

A. 0.01

B. 0.2%

C. 1%

D. 15%

E. 90%

Back 29

L2) D

Typically, about 15% of cells in animal tumors are found to be radiobiologically hypoxic.

Front 30

L3) If a tumor that is incapable of inducing angiogenesis begins as an avascular sphere of cells and receives oxygen only by diffusion from the vasculature and normal tissues at its periphery; the maximum diameter that this sphere could achieve without developing central necrosis would be approximately:

A. 20 nm

B. 20 μm

C. 0.2 mm

D. 2 mm

E. 20 mm

Back 30

L3) C

As oxygen diffuses through respiring tissue and is consumed by cells, the oxygen tension falls from that in human blood to essentially zero after a distance of approximately 100 microns (0.1 mm). This would produce a maximum radius of viable cells that this sphere could achieve with diameter = 2 X radius or 0.2 mm

Front 31

L4) Compared to patients with well-oxygenated tumors, patients with tumors that have low median values of pO2 have:

A. a reduced 5-year survival rate following either surgery or radiotherapy.

B. an increased 5-year survival rate following surgery alone.

C. an increased 5-year survival rate following combined modality therapy.

D. a decreased 5-year survival rate following radiotherapy alone, but increased survival after surgery alone.

E. an increased 5-year survival rate following radiotherapy alone, but decreased survival for surgery alone

Back 31

L4) 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.

Front 32

L5) 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 absence of reoxygenation, essentially all hypoxic cells will be eliminated 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 exceeds 1 mm.

Back 32

L5) B

Based on studies with rodent tumors, acute hypoxia results from transient blood flow due to the temporary closure of a blood vessel and therefore regions of acute hypoxia can exhibit rapid reoxygenation when the blood vessel re-opens. In contrast, regions of tumors distant from blood capillaries become chronically hypoxic and display relatively slow

reoxygenation. Without reoxygenation, it would be unlikely that a standard treatment dose would kill all hypoxic cells. As a tumor increases in size, the percentage of hypoxic cells generally increases or remains the same. Hypoxia develops when the distance between a cell and blood capillary exceeds about 100 μm.

Front 33

L6) Which statement about the tumor microenvironment is false?

A. Tumor-associated macrophages tend to localize to hypoxic regions.

B. Under physiological conditions, hypoxia is absent from normal tissues.

C. Hypoxia in tumors can result in decreased rates of cell proliferation.

D. High interstitial fluid pressure is a characteristic of solid tumors.

Back 33

L6) B

Hypoxia has been documented in the retina, thymus, myocardium and visual cortex.

Front 34

L7) Concerning angiogenesis, which of the following statements is TRUE?

A. Platelet-derived growth factor and fibroblast growth factor generally inhibit tumor angiogenesis.

B. All tumors require neovascularization to initiate growth.

C. The extent of tumor angiogenesis is a consistent predictor of tumor aggressiveness.

D. HIF-1α is the main transcriptional activator of VEGF.

E. In model systems, anti-angiogenesis agents have been shown to stimulate the development of metastases.

Back 34

L7) D

HIF-1α is the main transcriptional activator of VEGF. PDGF and bFGF stimulate angiogenesis. Some tumors, such as astrocytomas, can initiate growth by growing along normal blood vessels. The extent of angiogenesis is not a consistent predictor of tumor aggressiveness. Anti-angiogenesis agents may inhibit the development of metastases.

Front 35

L8) Normal regulation of angiogenesis involves a balance between pro- and anti-angiogenic factors. Which of the following descriptions of different angiogenic factors is incorrect?

A. FGF2 (bFGF) - Proangiogenic agent that behaves in a synergistic fashion with VEGF; may reduce endothelial cell apoptosis

B. Endostatin - Specific inhibitor of angiogenesis; induces endothelial apoptosis and migration.

C. IL-8 - Increases angiogenesis and metastasis

D. FGF7 (KGF) - Aids in angiogenesis by stimulating epithelial cell growth; receptor is a therapeutic target

E. Heparin - Potent pro-angiogenic agent, frequently upregulated in tumors; associated with radiation resistance

Back 35

L8) E

Heparin, a complex polysaccharide found in the matrices of numerous connective tissues, is a potent inhibitor of angiogenesis. In contrast, VEGF is an example of a pro-angiogenic agent that is frequently upregulated in tumors that is associated with radiation resistance.

Front 36

M1) Which pair of proteins plays a role in G1-phase cell cycle arrest following irradiation?

A. CDK1 and cyclin A

B. p53 and pRb

C. MSH-2 and MLH-1

D. rad 50 and RPA

E. CDK1 and cyclin B

Back 36

M1) B

p53 and the retinoblastoma protein (pRb) are involved in controlling G1 arrest, particularly after DNA damage. CDK1 and cyclin B are involved with the G2/M transitions. MSH-2 and MSLH-1 are associated with mismatch repair. Rad50 and RPA are involved with homologous recombinational repair of DNA double strand breaks.

Front 37

M2) All of the following statements concerning checkpoint surveillance mechanisms in the cell cycle following irradiation are correct, except that they:

A. are inhibitory pathways.

B. are signal transduction pathways.

C. occur as the result of DNA damage that causes induction of cell cycle progression inhibitors.

D. serve primarily as a means of stopping cells from progressing into M phase.

E. are a way by which cells solve problems related to completion of cell division.

Back 37

M2) D

Checkpoint surveillance in cells following irradiation serves to regulate entry into and through S phase as well.

Front 38

M3) An asynchronous population of cells is exposed to 2 Gy X-rays. Immediately after exposure, the cell cycle distribution among the cells destined to survive is:

A. unchanged.

B. enriched with G1- and G2/M-phase cells.

C. reduced in S-phase cells.

D. enriched with S-phase cells.

E. reduced equally in all cell cycle phases.

Back 38

M3) D

Cells in radiosensitive phases of the cell cycle will be selectively killed leaving an increased proportion of resistant S-phase cells that survive.

Front 39

M4) If the TS, LI and λ (the correction factor for the non-linear distribution of cells throughout the cell cycle) of a specific tumor are 7.5 hours, 0.05 and 0.8, respectively, the Tpot of that tumor will be:

A. 0.4 hour

B. 15 hours

C. 3 days

D. 5 days

E. 8 days

Back 39

M4) D

The Tpot can be determined from the equation Tpot = λTs/LI = 0.8 X 7.5/0.05 = 120 hours = 5 days.

Front 40

M5) The best explanation for the observation that the potential doubling time of a tumor is rarely achieved is:

A. the long cell cycle time for most tumor cells.

B. a high cell loss factor.

C. the long duration of mitosis in tumor cells.

D. a small tumor growth fraction.

E. the large population of hypoxic cells that are no longer clonogenic

Back 40

M5) B

Cell loss is the major factor to explain differences between tumor doubling time and Tpot.

Front 41

M6) All of the following statements concerning tumor kinetics are true, except:

A. The potential doubling time (Tpot) of a tumor is defined as the doubling time that the tumor population would have in the absence of cell loss.

B. Tpot is usually shorter than the measured tumor volume doubling time.

C. The mean cell-cycle time will usually be greater than the Tpot because of the presence of non-proliferating cells.

D. An estimate of Tpot can be obtained from values of the labeling index and the duration of DNA synthesis.

E. For most tumor cells, there is less variation in the duration of S phase than in the overall cell cycle time.

Back 41

M6) C

The mean cell cycle (Tc) will be shorter than the Tpot as some cells may not be actively proliferating.

Front 42

N1) The impact of mutant p53 upon cellular radiation response includes all of the following, except:

A. decreased G1/S phase delay

B. increased apoptosis

C. altered DNA repair

D. increased radioresistance of cells with a pro-apoptotic tendency

E. decreased p21 levels

Back 42

N1) B

In many cell lines, wild type p53 facilitates cell entry into apoptosis.

Front 43

N2) p53 causes transcriptional activation of:

A. p16

B. bax

C. DNA-PKcs

D. ATM

E. BRCA2

Back 43

N2) B

p53 stimulates bax activity which is pro-apoptotic.

Front 44

N3) Concerning radiation-induced changes in gene expression, which of the following statements is TRUE?

A. The same dose of radiation will induce nearly identical gene expression profiles in different target tissues.

B. Microarray studies have shown that most genes induced by ionizing radiation are regulated by p53.

C. Ionizing radiation induces the expression of genes involved in DNA double strand break repair as well as those involved in nucleotide excision repair (NER).

D. The transcriptional profiles of genes induced immediately after exposure to ionizing radiation rarely differ from those observed hours or days later.

E. Genes involved in cell cycle regulation are usually down-regulated by ionizing radiation.

Back 44

N3) C

Many microarray studies have shown that ionizing radiation up-regulates NER genes in addition to genes which encode products associated with the repair of double strand breaks. This is somewhat unexpected as NER is classically associated with UV damage repair. A particular dose of radiation will stimulate differentially many genes. Ionizing radiation induces the expression of some genes whose regulation is p53-independent, but it is not correct that most genes induced by ionizing radiation are regulated by p53. The genes induced immediately following irradiation differ from those expressed at a later point. Some genes involved in cell cycle regulation are up-regulated by ionizing radiation.

Front 45

N4) Which of the following is NOT associated with cellular radioresistance?

A. Bcl-2 overexpression

B. Ras activating mutation

C. High levels of pimonidazole staining

D. Her2/neu overexpression

E. BRCA2 mutations

Back 45

N4) E

Mutations in BRCA2 are associated with cellular radiosensitivity. Bcl-2 is anti-apoptotic. Ras and Her2/neu overexpression are associated with radioresistance. High levels of pimonidazole indicate the presence of hypoxia presumably associated with tumors.

Front 46

N5) A human genetic disease associated with the loss of cell cycle regulation and extreme sensitivity to ionizing radiation is:

A. Bloom syndrome

B. Ataxia telangiectasia

C. Fanconi anemia

D. Hereditary nonpolyposis colorectal cancer

E. Xeroderma pigmentosum

Back 46

N5) B Cells from individuals with ataxia telangiectasia are highly sensitive to ionizing radiation and lack the G1/S, S, and G2 checkpoints in response to ionizing radiation.

Front 47

N6) Cyclins are:

A. lipid kinases.

B. protein phosphatases.

C. regulatory proteins for CDKs.

D. present only in the G0 phase of the cell cycle.

E. regulators of DNA repair

Back 47

N6) C

Cyclins increase and decrease in level through the cell cycle, with different cyclins being increased at different phases of the cell cycle. They bind to cyclin-dependent kinases (CDKs) to form the active complexes involved in cell cycle regulation.

Front 48

N8) In cells exposed to ionizing radiation at conventional dose rates, ATM:

A. is deacetylated and therefore inactivated.

B. is phosphorylated and thus activated.

C. levels decrease.

D. dephosphorylates γ-H2AX.

E. ubiquitinates siRNA.

Back 48

N8) B

After ionizing radiation exposure, ATM is activated by phosphorylation. None of the other alterations have been observed.

Front 49

N7) Bloom syndrome is due to a mutation in a:

A. protein kinase.

B. DNA ligase.

C. DNA helicase.

D. DNA binding protein.

E. bcl-2 family member.

Back 49

C

The protein produced by the Bloom syndrome gene (BLN) is a DNA helicase, involved in DNA unwinding