Chromosome and Chromatid Damage Flashcards
Which of the following statements concerning chromosome aberrations produced in cells after whole body X-irradiation is TRUE?
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
D
Spectral karyotyping (SKY) uses fluorescence staining of chromosomes employing uniquely-colored probes specific for individual chromosomes, thus allowing them to be distinguished from each other on the basis of color. Stable translocations are revealed using SKY as a single chromosome that appears to be multi-colored.
The formation of terminal deletions follows a linear dose response since these are single-hit aberrations (Answer Choice A).
Translocations can be stable aberrations since they do not necessarily lead to cell death (Answer Choice B).
The number of dicentric chromosomes detected in peripheral blood lymphocytes decreases with time after irradiation since these are unstable aberrations that ultimately cause the death of the lymphocyte progenitors and stem cells (Answer Choice C).
The minimum dose that can be detected through scoring dicentric chromosomes is roughly 0.25 Gy (Answer Choice E).
Which of the following types of chromosome aberrations are most responsible for the formation of micronuclei observed after irradiation?
A. Sister chromatid exchanges
B. Chromatid gaps
C. Inversions
D. Quadriradials
E. Acentric fragments
E
Micronuclei are created due to the presence of acentric fragments, which form in the progeny of irradiated cells that undergo mitosis in the presence of one or more symmetrical chromosome aberrations. Sister chromatid exchanges are reciprocal exchanges between chromatids of the same chromosome that are not readily induced by ionizing radiation (Answer Choice A).
Chromatid gaps appear as loss of genetic material from a single chromatid arm and may be caused by incomplete breaks (Answer Choice B).
Inversions result when two breaks are produced in a single chromosome and the resulting excised chromosomal fragment reinserts itself back into the chromosome, but with the opposite polarity (Answer Choice C).
A quadriradial is a chromatid-type aberration that may arise from illegitimate interchromosomal recombination, accompanied by crossing-over (Answer Choice D).
Which of the following is the most reliable 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
D
Individual chromosome aberrations can, in general, be detected readily only during mitosis. However, some chromosome aberrations lead to the formation of micronuclei, which develop when a pseudo nuclear membrane forms around acentric chromosome fragments or whole chromosomes that did not segregate properly into daughter cells during the previous mitosis. Micronuclei are observed in peripheral lymphocytes and thus can be seen in interphase cells.
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 terminal deletion
B. The induction and interaction of DNA double-strand breaks is the principal mechanism for the production of chromosome aberrations
C. Dicentrics, acentric rings, and translocations are formed following X-irradiation of cells in the G0/G1 phase of the cell cycle, and their formation follows 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
E
Chromatid type aberrations are produced in cells only when irradiation follows DNA synthesis in S phase. In this case, only one of the two chromatid has the anomaly. Anaphase bridges are caused by chromatid type aberrations. Chromosomal type aberrations are produced when irradiaiton occurs prior to DNA synthesis and the anomaly is duplicated on both chromatids of the chromosome. Examples included dicentric or ring chromosomes.
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
A
The formation of dicentric chromosomes is linear at low radiation doses but follows a quadratic function at higher doses. Two distinct mechanisms are thought to be responsible for these two components of the linear-quadratic dose response curve. The linear portion of the dose response relationship is assumed to result from the simultaneous induction of two chromosome breaks by a single track. The quadratic portion is assumed to result from the two chromosome breaks being produced by two separate radiation tracks.
Which of the following statements concerning chromosome aberrations is TRUE?
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
D
Terminal deletions are induced as a linear function of dose since they result from a single chromosomal break.
A ring chromosome is an example of a chromosome-type aberration, not a chromatid-type aberration (Answer Choice A).
A dicentric is an unstable aberration since it results in the formation of an acentric fragment and ultimately causes cell death (Answer Choice B).
Breaks in two chromatids, followed by illegitimate rejoining, produce an anaphase bridge (Answer Choice C).
The yield of dicentric chromosomes increases with increasing dose-rate for low LET radiation (Answer Choice E)
Increased numbers of chromosome aberrations, especially quadriradials, are frequently found even in the absence of radiation in which of the following human syndromes?
A. Xeroderma pigmentosum
B. Fanconi anemia
C. Cockayne’s syndrome
D. Niemann-Pick disease
E. Li-Fraumeni syndrome
B
Blood cells from individuals with Fanconi anemia, an autosomal recessive disorder, are harboring a mutation in one of 22 FANC genes, which are part of the FA/BRCA pathway. Defects in this pathway result in chromosomal instability due to decreased capacity to repair interstrand DNA crosslinks. This results in the development of high numbers of chromosome aberrations, especially quadriradials. These complex aberrations increase dramatically with exposure to DNA cross-linking agents such as mitomycin c.
