RB Astro topic 2 Flashcards

1
Q

What is the primary target of radiation damage in cells?

A

Nuclear DNA

Nuclear DNA is considered the most important target for radiation damage due to its structure and the consequences of damage.

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2
Q

What are the possible outcomes of DNA damage due to ionizing radiation?

A
  • DNA repair
  • DNA mutations
  • Cell death
  • Acute radiation toxicities
  • Late tissue toxicities
  • Developmental effects in the fetus
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3
Q

True or False: Mitochondrial DNA is more important than nuclear DNA in terms of radiation damage.

A

False

Mitochondrial DNA is less important because it has multiple copies and damage to a few does not significantly impact cell function.

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4
Q

What is the most common type of DNA damage caused by radiation?

A

Base damage

Base damage is easily repaired and is the most frequent type of damage encountered.

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5
Q

What are the two types of DNA repair pathways discussed?

A
  • Homologous recombination (error-free)
  • Non-homologous end joining (error-prone)
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6
Q

Fill in the blank: The repair of single strand breaks is typically carried out by _______.

A

Base excision repair

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7
Q

What is considered a double strand break in DNA?

A

Two single strand breaks that are close to each other

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8
Q

What is a multi-damage site (MDS)?

A

A combination of damage within a 20 base size or a 10 nanometer diameter volume of chromatin

MDS can include various types of damage like single strand breaks, double strand breaks, and base damage.

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9
Q

What is the consequence of a double strand break in DNA?

A

Loss of genetic material and potential mutations

Double strand breaks can lead to errors in DNA repair processes, resulting in mutations.

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10
Q

What is the term for damage that occurs when DNA strands do not join together correctly after a double strand break?

A

Illegitimate recombination

This process can lead to significant mutations and loss of protein function.

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11
Q

What type of radiation is most likely to produce complex lesions?

A

High LET radiation

Complex lesions can also occur from low LET radiation but are more commonly associated with high LET radiation.

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12
Q

What happens during homologous recombination repair?

A

A double strand break uses a duplicate of its chromosome to repair itself.

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13
Q

What are the typical phases of the cell cycle where most DNA repairs occur?

A
  • G0
  • G1
  • Early S phase

These phases are less favorable for homologous recombination since duplication of the chromosome occurs in late S and G2 phase.

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14
Q

What is the relationship between ionizing radiation and free radicals?

A

Ionizing radiation can lead to free radical formation, which can further damage DNA.

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15
Q

What is the significance of clustered lesions in radiation damage?

A

They involve multiple types of damage in a small area, complicating the repair process.

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16
Q

What is the D0 dose for mammalian cells and its expected damage outcomes?

A

1 to 2 gray

At this dose, expect over 1,000 base damage lesions, 1,000 single strand breaks, and around 40 double strand breaks.

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17
Q

True or False: Single strand breaks are more damaging than double strand breaks.

A

False

Single strand breaks are easier to repair and less harmful than double strand breaks.

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18
Q

What is the expected damage from radiation exposure?

A

1,000 to 2,000 damage bases, 1,000 single strand breaks, 40 double strand breaks

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19
Q

What does a D0 dose refer to in radiation exposure?

A

One gray (but not exactly one gray)

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20
Q

What types of damage are primarily caused by gamma rays and x-rays?

A
  • Single base damage
  • Single strand breaks
  • Double strand breaks
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21
Q

What types of damage are primarily caused by UV radiation?

A
  • TT dimers
  • Cyclobutylperminine dimers
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22
Q

What is the difference between alkaline and neutral solutions in measuring DNA strand breaks?

A

Alkaline detects single strand breaks and double strand breaks; neutral detects only double strand breaks

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23
Q

What is the purpose of the filter elution assay?

A

To distinguish between single strand breaks and double strand breaks

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24
Q

How does the comet assay work?

A

Measures broken DNA by observing the formation of a comet tail when an electric current is applied

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25
What does a micronucleus contain?
An acentric fragment
26
What type of cell phase is most often analyzed for chromosomal injury?
M-phase cells
27
What is a dicentric chromosome?
A chromosome with two centromeres
28
What is the difference between chromosomal and chromatid aberrations?
* Chromosomal damage occurs in G0, G1, or early S * Chromatid damage occurs in late S or G2
29
What is the significance of the centromere during cell division?
It plays a critical role in the alignment of chromosomes at the equatorial plate
30
What is the typical structure of human chromosomes?
Consists of a short arm (P-arm) and a long arm (Q-arm) with coding regions that vary in gene density
31
What is the common assay used for measuring DNA damage?
Microgel electrophoresis system
32
What are the two arms of a chromosome called?
* P-arm (short arm) * Q-arm (long arm)
33
What is the typical result of radiation exposure on chromosomes?
Acentric fragments and dicentric chromosomes
34
What is the primary function of histones in relation to DNA?
Histones associate with DNA to form chromatin
35
What is the function of the telomere?
Protects the ends of chromosomes from deterioration
36
Fill in the blank: The __________ assay is used to measure chromosome injury by counting micronuclei.
micronucleus
37
True or False: The micronucleus assay is universally accepted and without controversy.
False
38
What is the typical sensitivity of the alkaline comet assay?
Most sensitive for detecting single strand breaks
39
How does pulse field gel electrophoresis differ from standard gel electrophoresis?
It uses a zigzag current to separate large fragments of DNA
40
What factors can influence the impact of radiation damage on a chromosome?
Location of damage within gene-rich or gene-poor regions
41
What is the importance of monitoring DNA repair over time?
It indicates the efficiency of the repair mechanisms in response to damage
42
What is the common method used to stimulate cells for detection in M phase?
Hemagglutinin
43
What are the phases of M phase that can be observed under a light microscope?
Prophase and telophase
44
What critical role does the centromere play during cell division?
It allows chromosomes to line up at the equatorial plate and facilitates their movement into daughter cells
45
What happens to a chromosome that has a centromere during cell division?
It gets pulled into the daughter cells
46
What is a dicentric chromosome?
A chromosome with two breaks that joins with another chromosome, resulting in two centromeres
47
What is an acentric fragment?
A chromosome fragment that lacks a centromere
48
What is the fate of an acentric fragment during cell division?
It is lost and cannot bind to a spindle fiber
49
What is the second most common lethal chromosomal aberration?
Ring chromosome
50
Why is a dicentric chromosome more common than a ring chromosome?
Two hits in two chromosomes are more likely than two hits in the same chromosome
51
What is an anaphase bridge?
A chromatid aberration that looks like a bridge during anaphase
52
What are the three lethal chromosomal aberrations mentioned?
* Dicentric * Ring * Anaphase bridge
53
What distinguishes symmetrical aberrations from asymmetrical aberrations?
Symmetrical aberrations retain all of the regal DNA, while asymmetrical ones result in DNA loss
54
What is a symmetrical translocation?
A rearrangement where two chromosomes exchange DNA without significant loss or gain
55
What can small deletions lead to in terms of cellular outcomes?
Loss of a tumor suppressor gene, potentially leading to cancer
56
What is an inversion in chromosomal terms?
A rearrangement where a segment of DNA flips over within the same chromosome
57
What are the non-lethal chromosomal aberrations mentioned?
* Symmetrical translocation * Small deletion * Inversion
58
What is the relationship between chromosome aberrations and radiation exposure?
Chromosome aberrations are directly related to radiation dose
59
What is the best marker for assessing radiation exposure in the first six months after an accident?
Dicentrics
60
What method is used to detect chromosomal aberrations using fluorescent probes?
Fluorescence in situ hybridization (FISH)
61
What is spectral karyotyping (SKY)?
A method that colors chromosomes to visualize rearrangements
62
What are the effects of chromosome aberrations on health?
They can correlate with physical abnormalities, mental retardation, and cancer
63
True or False: Mental retardation can only be classified as a stochastic effect.
False
64
Fill in the blank: A _______ effect is one that happens by chance and can involve a single cell effect.
stochastic
65
What type of chromosomal aberration involves breaks occurring after DNA duplication?
Chromatid aberrations
66
What is the most common consequence of a dicentric chromosome?
The cell is destined to die
67
What is the significance of determining the background rate of translocations in a population?
It helps in assessing radiation exposure and its effects
68
What is spectral carrier typing (SKY)?
A method that uses different colors for probes specific to each chromosome to visualize rearrangements. ## Footnote Also known as chromosome painting.
69
How does spectral carrier typing help in identifying chromosomal abnormalities?
It allows for immediate identification of rearranged chromosomes through a multi-colored image. ## Footnote This technique can detect abnormalities not visible in standard chromosome smears.
70
What does the linear quadratic model describe?
The relationship between absorbed dose and the number of dicentric chromosomes per cell. ## Footnote It combines linear and quadratic relationships.
71
What is the significance of dicentric chromosomes in radiation studies?
They indicate chromosomal damage and relate to cell killing and survival. ## Footnote Dicentrics are particularly relevant in the context of radiation exposure.
72
What is gamma H2AX?
A phosphorylated histone protein that indicates DNA damage and repair. ## Footnote Its presence signifies that cells have been irradiated and are undergoing repair.
73
What does the gamma H2AX assay measure?
It measures the presence of gamma H2AX foci, indicating DNA repair processes. ## Footnote This assay is sensitive for detecting damage from radiation.
74
What is the relationship between cell ploidy and radiosensitivity?
Haploid cells are most radiosensitive due to having only one copy of each repair gene. ## Footnote Diploid cells are less sensitive, while tetraploid and hexaploid cells are more resistant.
75
Which cells are categorized as most radio-sensitive?
Vegetative intermitotic cells, which are dividing and undifferentiated. ## Footnote These include stem cells.
76
What is the exception to the rule of radio sensitivity based on differentiation and division?
Lymphocytes are highly radio-sensitive despite being reverting post-mitotic cells. ## Footnote They do not typically divide until activated by an antigen.
77
What types of chromosomal aberrations are typically lethal?
Lethal aberrations include rings, dicentrics, and anaphase bridges. ## Footnote Non-lethal aberrations include reciprocal translocations, small deletions, and inversions.
78
What does the yield of dicentrics equal in the linear quadratic model?
Yield = alpha times dose + beta times dose squared. ## Footnote Alpha and beta are constants related to the effects of radiation.
79
What is the primary focus of the gamma H2AX assay?
To detect DNA repair processes as a reflection of DNA damage. ## Footnote It is not a direct measure of DNA damage but indicates the presence of repair machinery.
80
Fill in the blank: The _______ is a common method for detecting chromosomal aberrations.
gamma H2AX assay.
81
True or False: The gamma H2AX assay is useful for immediate assessment of radiation exposure in accidents.
False. ## Footnote The gamma H2AX signal disappears hours after exposure, making it less useful in emergencies.