Rabex 2005 Part D,e,f

Front 1

D1) 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 involve 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.

Back 1

D1) 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.

Front 2

D2) Which one of the following statements concerning the appearance of abnormal chromosomes following irradiation is incorrect?
A. Chromatid-type aberrations arise from irradiation during or after S-phase.
B. Dicentrics are a type of asymmetrical exchange.
C. Chromosome aberrations visible at mitosis are unlikely to have biological consequence.
D. Asymmetrical exchanges result in the formation of acentric fragments that appear as micronuclei in daughter cells.
E. The yield (y) of dicentrics following the exposure of cells to low-LET radiation can be modeled using the equation y = αD + βD2 where D is the dose and α and β are constants.

Back 2

D2) C

Chromosome aberrations observed at the first mitosis after irradiation are one of the best correlates for ultimate cell lethalilty.

Front 3

D3) Which of the following statements concerning radiation-induced chromosomal aberrations is TRUE?:

A. The lowest dose after which radiation exposure can be detected through examination of peripheral blood lymphocytes after recent whole body doses is approximately 2 Gy.

B. Irradiation of cells prior to DNA synthesis results in chromatid-type aberrations.

C. An anaphase bridge is a common chromosome-type aberration.

D. The induction of dicentric chromosomes by low LET radiation follows a linear-quadratic dose response.

E. Radiation-induced chromosomal translocations usually result in cellular lethality.

Back 3

D3) D

The induction of dicentric chromosomes follows as linear-quadratic dose response. Dicentrics can be detected and are used to approximate doses for whole body exposures as low as 0.25 Gy. An anaphase bridge is a chromatid-type aberration. Dicentric chromosomes represent a chromosome-type aberration. Radiation-induced chromosomal translocations are generally stable and do not normally lead to lethality

Front 4

D4) During the previous week an individual is suspected of receiving a whole body X-ray dose of 1 Gy. The most reliable indicator of exposure would be quantitation of:
A. DNA double-strand breaks.
B. DNA nucleotide excision repair enzymes.
C. sister chromatid exchanges.
D. DNA minisatellites.
E. chromosomal aberrations at mitosis.

Back 4

D4) E

Analysis of metaphase chromosome rearrangements is a sensitive and reliable biodosimeter for doses as low as ~25 cGy. Most double strand breaks induced during the previous week would have already been repaired at the time of testing.

Front 5

D5) The most reliable method for identification of symmetrical chromosome rearrangements is:
A. sister chromatid exchange.
B. spectral karyotyping.
C. fluorescence in situ hybridization (FISH).
D. premature chromosome condensation.
E. pulsed field gel electrophoresis.

Back 5

D5) C

Symmetrical chromosome rearrangements include reciprocal translocations and can be detected reliably only with fluorescence in situ hybridization.

Front 6

D6) 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 β-component of dose response curves.
E. result from single lethal hits.

Back 6

D6) D

Two-hit aberrations (or DNA breaks) are dependent on the square of the dose; hence they are the β (quadratic) component of the dose response curve and will decrease with dose fractionation or decreasing dose rate, both of which allow time for repair.

Front 7

D7) Which type of chromosome aberration predominates following exposure to low doses of ionizing radiation?
A. Dicentrics
B. Translocations
C. Rings
D. Terminal deletions
E. Interstitial deletions

Back 7

D7) D

Single hit kinetics predominates at low doses of ionizing radiation. Terminal deletions involve a single double-strand break and therefore follow single-hit kinetics. All of the other chromosome aberrations listed involve two double-strand breaks and therefore follow two-hit kinetics.

Front 8

D8) Which of the following chromosome aberrations is most appropriate to use for detection of exposure to ionizing radiation many following a possible irradiation?
A. Reciprocal translocations
B. Rings
C. Dicentrics
D. Chromosome breaks
E. Chromatid breaks

Back 8

D8) A

Reciprocal translocations are relatively stable chromosome aberrations and therefore can be detected at long times after exposure to ionizing radiation. All of the other chromosome aberrations are highly unstable or short-lived and therefore can only be detected for one or a few cell generations after exposure.

Front 9

E1) Radiation-induced apoptosis is a process by which damaged cells:
A. perform DNA repair.
B. die in S-phase.
C. are systematically dismantled and are phagocytized by adjacent cells.
D. die in G1-phase by exploding/bursting.
E. cause inflammation in surrounding tissue.

Back 9

E1) C

Apoptosis is a cell death process that involves a systematic dismantling of cells and the fragmentation of nuclear and genetic material. It is not a repair process. Cells do not die specifically in S phase. Apoptotic cells do not swell and burst or cause inflammation as observed in necrotic cells. Apoptosis is a process of programmed cell death, which is very tightly regulated. Some of the characteristics are chromatin condensation and DNA fragmentation due to the activation of specific endonucleases that cut the DNA at the linker region between nucleosomes, leading to the formation of fragments that are multiples of units comprising 180-200 bp. In necrosis, there usually is random cleavage of DNA resulting in mixture of different sizes of fragments. An early event occurring in apoptosis is the flipping of phosphatidyl-serine from the inner plasma membrane to the outer leaflet of the plasma membrane. Apoptosis is a physiological process involving single cells while necrosis is a non-physiological death involving a number of cells in an area and associated with development of inflammation. The apoptotic pathway is a highly conserved pathway and the specific apoptotic genes were originally discovered in the worm C. elegans. The first genes to be discovered were the ones that encode for a family of proteases, named caspases. There are two major types of caspases involved in the apoptotic process: initiator caspases and executioner caspases.

Front 10

E2) 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

Back 10

E2) C

Apoptosis does not stimulate an inflammatory response.

Front 11

E3) Concerning apoptosis, the following statements are true, except it:
A. is dependent upon caspase activation.
B. occurs after relatively low doses of radiation.
C. can be initiated as early as 3 hours post-irradiation.
D. occurs via an extrinsic pathway as a result of mitochondrial damage
E. occurs in terminally differentiated, non-cycling cells.

Back 11

E3) D

Apoptosis occurs via the intrinsic pathway as a result of mitochondrial damage.

Front 12

E4) The assay most appropriate to investigate loss of cell membrane integrity after irradiation is:

A. trypan blue dye exclusion.

B. malondialdehyde production.

C. comet assay.

D. neutral elution.

E. pulsed-field gel electrophoresis.

Back 12

E4) A

Trypan blue staining is the best measure of the cell membrane integrity.

Front 13

E5) Which of the following is NOT a characteristic of apoptosis?
A. DNA laddering
B. Activation of caspases
C. Formation of membrane-enclosed bodies
D. Cell swelling
E. Phagocytosis

Back 13

E5) D

Cells undergoing apoptosis exhibit shrinkage and condensation, not swelling.

Front 14

E6) Autophagy is:
A. an unregulated 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.

Back 14

E6) D

Autophagy or type II programmed cell death is a tightly regulated, ordered cell death process that is a response to nutrient deprivation, hypoxia, crowding, senescence 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). Autophagy has a morphology distinct from cells undergoing either apoptosis or necrosis. There is increased endocytosis, vacuolation, membrane blebbing, nuclear condensation, but no caspase activation. It appears to be a defensive reaction that can lead to cell death

Front 15

E7) The role of the apoptotic process in development is principally to:
A. protect cells from viral infection.
B. selectively kill cells so as to sculpt body parts.
C. protect cells from oxidative stress.
D. prevent inflammation.
E. facilitate DNA repair processes.

Back 15

E7) B

Apoptosis plays an important role in the morphological aspects of development.

Front 16

E8) Radiation-induced apoptosis occurs in:
A. normal tissues and tumors.
B. only in normal tissues.
C. only in tumors.
D. only in the thymus.
E. only in lymphocytes.

Back 16

E8) A

Apoptosis can occur in normal as well as cancer cells.

Front 17

E9) 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.

Back 17

E9) 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.

Front 18

F1) Till and McCulloch developed an assay for measuring the survival of pluripotent hematopoietic stem cells based on their ability to:
A. repopulate marrow.
B. allow recipient mice to survive.
C. form colonies in spleens.
D. take up tritiated thymidine.
E. form colonies in cell culture.

Back 18

F1) C

The spleen colony assay developed by Till and McCulloch tested the ability of bone marrow cells removed from a donor animal to form colonies in the spleens of irradiated recipients. Although the recipient animals were lethally irradiated, the quantitative measurement of cell survival resulted from counting the number of colonies formed prior to animal death, and not from enumerating the proportion of mice that survived.