moo Flashcards
(168 cards)
1
Q
What are the 5 main types of DNA damage from radiation?
A
- Base damage
- Single-strand breaks (SSB)
- Double-strand breaks (DSB)
- Crosslinking (DNA-DNA or DNA-protein)
- Clustered
2
Q
What are the two main pathways for DSB repair?
A
- Homologous Recombination Repair (HRR) - accurate, uses template
- Non-Homologous End Joining (NHEJ) - error-prone, no template
3
Q
What protein signals DNA damage and phosphorylates H2AX?
A
ATM (Ataxia Telangiectasia Mutated)
4
Q
What is the equation for the Linear Quadratic (LQ) model?
A
SF = exp(-(αD + βD²))
5
Q
Which survival model has a ‘shoulder’ and why?
A
LQ model - reflects sublethal damage repair
6
Q
What does D₀ represent in the single target, single hit model?
A
Dose required to reduce survival to 37%
7
Q
What is the equation for BED?
A
BED = D * (1 + d / (α/β))
8
Q
What is the equation for EQD2?
A
EQD2 = BED / (1 + 2 / (α/β))
9
Q
What is the formula for TCP assuming N₀ clonogenic cells?
A
TCP = exp(-N₀ * SF)
10
Q
What are the 5 Rs of radiotherapy?
A
Repair, Reoxygenation, Redistribution, Repopulation, Radiosensitivity
11
Q
What does SF2 indicate?
A
Surviving fraction after 2 Gy - a measure of radiosensitivity
12
Q
What dose range causes hematopoietic syndrome?
A
2–5 Gy
13
Q
What dose causes gastrointestinal syndrome?
A
> 10 Gy
14
Q
What dose causes cerebrovascular syndrome?
A
> 100 Gy
15
Q
What is the LNT model assumption?
A
Linear risk with no threshold
16
Q
What is DDREF and typical value?
A
Dose & dose-rate effectiveness factor, ~2
17
Q
What is the baseline congenital defect risk?
A
3%
18
Q
What is the doubling dose for genetic effects?
A
1 Gy
19
Q
What is the Oxygen Enhancement Ratio (OER)?
A
OER = Dose in hypoxia / Dose in oxygenated
OER ~3 for low LET
20
Q
How does LET affect RBE and OER?
A
High LET → High RBE, Low OER
21
Q
What is a deterministic effect?
A
Has threshold, severity increases with dose
22
Q
What is a stochastic effect?
A
No threshold, probability increases with dose
23
Q
What is the bystander effect?
A
Non-irradiated cells near irradiated ones show damage
24
Q
What is the abscopal effect?
A
Distant tumour response due to immune signalling
25
What is genomic instability?
Delayed effects in progeny of irradiated cells
26
What are serial organs and their risk profile?
e.g., spinal cord - one damaged unit → full organ failure
27
What are parallel organs and their risk profile?
e.g., lung - damage is partial/fractional
28
What determines NTCP?
Volume, dose, organ structure (serial vs parallel)
29
Why does RBE fall at very high LET?
Energy is wasted killing already-dead cells → RBE drops (overkill effect).
30
Why doesn't RBE plateau instead of fall?
Extra dose gives no extra kill → RBE = reference dose / (too much test dose).
31
If LET increases, does dose increase?
No. LET = energy per length, dose = energy per mass.
32
Difference between LET and dose?
LET = quality (keV/μm), dose = quantity (Gy).
33
Why does high LET lower OER?
High LET causes direct DNA damage — needs no oxygen.
34
Why is RBE highest at ~100 keV/μm?
Ionisations match DNA width → max complex damage.
35
What is the abscopal effect?
Distant tumour shrinkage after local RT, via immune activation.
36
What are the 4 most important factors about radiation exposure?
1. Where was it
2. How long ago
3. How long was it
4. What type of radiation
37
What is a somatic effect?
One felt by the individual
38
What is a genetic effect?
One expressed in the offspring
39
What is cell physiology?
The activities that keep a cell functioning and alive
40
What is an indirect hit?
When the radiation interacts with a charged particle (Rather than the DNA) that will later cause damage
41
What are the 2 methods of indirect radiation hits?
Cherenkow (PP) and Bremmsstrahlung (Compton)
42
What is the method of direct radiation hits?
Ionisation (PEE)
43
What is the relationship between PEE and z?
cubed
44
What is the relationship between PP and z?
squared
45
What is the relationship between Compton and z?
linear
46
Is ionisation related to cell death?
No
47
How does photonic radiation damage happen?
Indirect interactions -- free radicals
48
What is the formula for diffusion distance?
49
What is the significance of a short diffusion distance?
more spatially localised damage
50
What does radiation epidemiology study?
It studies how ionizing radiation exposure affects human health, especially cancer risk.
51
What is a cohort study?
Follows two groups (exposed vs control) over time to compare disease rates.
52
What is a case-control study?
Compares people with disease (cases) to those without (controls), looking back at exposure history.
53
What does Relative Risk (RR) represent?
The ratio of disease risk in the exposed group vs the control group.
54
How is RR calculated?
RR = Rate in exposed group / Rate in control group.
55
What does RR = 1 mean?
No increased risk from exposure.
56
What is Excess Relative Risk (ERR)?
ERR = RR - 1; the extra risk due to radiation.
57
What does ERR = 0.5 mean?
A 50% increase in risk due to radiation.
58
What is Attributable Risk (AR)?
The proportion of disease in the population caused by exposure.
59
AR formula?
AR = P(RR - 1) / [P(RR - 1) + 1], where P = % of population exposed.
60
What is the LNT model?
Linear No-Threshold: assumes cancer risk increases linearly with dose, no safe threshold.
61
Why is the LNT model controversial?
Data from high background radiation areas don’t always support it.
62
What is DDREF?
Dose and Dose Rate Effectiveness Factor — reduces risk estimates for low dose/rate exposures.
63
Typical value of DDREF?
2 (i.e., low-dose risk = half of high-dose risk).
64
What is EAR?
Excess Absolute Risk — adds a number of extra cases to the baseline risk.
65
What is ERR (in projection models)?
Excess Relative Risk — multiplies baseline risk by a factor.
66
What is the main dataset used in radiation epidemiology?
Atomic bomb survivor data.
67
What are the limitations of atomic bomb data?
It was high dose and acute; not ideal for modeling chronic low-dose risk.
68
What is 1 Sievert (Sv) approximately equal to in risk?
~5% chance of fatal cancer.
69
What is the cancer risk from 1 mSv?
About 1 in 20,000.
70
What is Tc in cell kinetics?
The total cell cycle time (duration of one full cycle of cell division).
71
What does T_(pot) represent?
Potential doubling time — how fast the tumor could double if there were no cell loss.
72
What is the formula for T_(pot)?
where GF is the fraction of cells in the cycle.
73
What is T_D?
Volume doubling time — the actual time it takes for the tumor volume to double.
74
What is the natural cell loss factor phi?
the loss rate / birth rate of cells
75
What is T_(eff)?
Effective doubling time
76
What does the power law assume?
Each division produces 2 daughter cells.
77
What does the exponential growth equation look like?
Kg is the effective growth rate.
78
How is the effective growth rate k_g defined?
k _ B - k _ L, where k_B is the birth rate and k_L is the loss rate.
79
What does k_{\text{eff}} = 0 imply?
Cell birth and loss are balanced — no net growth.
80
How does repopulation affect BED?
It reduces BED:
BED = D\left(1 + \frac{d}{\alpha/\beta}\right) - kT
Where k is repopulation rate and T is time.
81
What does the BED equation account for during treatment?
Cell kill and repopulation.
82
What’s the effect of hypoxia on BED?
BED is reduced:
BED = (1 + \text{hypoxia scaling factor}) \cdot \text{original BED}
83
What is the equation for volume doubling time?
84
What is the expression for effective doubling time?
85
What is the repopulation factor (equation?)
86
How do you apply the hypoxia factor (q) to BED?
Divide any dose term (d or D) by q
87
What are the 4 possible outcomes of damaged DNA?
Repair, senescence, death, or mutation.
88
What is senescence?
A state where the cell remains alive but permanently stops dividing.
89
What are the 3 types of mutations that can result from DNA damage?
Somatic, germline, and fetal.
90
What does a somatic mutation affect?
Non-reproductive body cells — can lead to cancer.
91
What does a germline mutation affect?
Reproductive cells — can be passed to offspring.
92
What is a fetal mutation?
A mutation that occurs in utero, during pregnancy.
93
How is cell death related to DNA damage?
It increases logarithmically with the number of damaged DNA sites.
94
Why does more DNA mean more radiosensitivity?
More DNA = higher chance of radiation hitting something critical → less dose needed to cause damage.
95
What connects the strands in the DNA double helix?
Hydrogen bonds between complementary bases.
96
What determines DNA’s 3D shape (conformation)?
Hydration state.
97
What bonds connect adjacent bases on the same DNA strand?
Pi-bonds and pi-stacking interactions.
98
What happens when ionizing radiation damages electrons in DNA?
The electrons can migrate — causing or repairing further damage.
99
What is chromatin?
DNA wrapped around histones, plus associated proteins.
100
What role does chromatin play in damage repair?
Gives structure and helps prevent/repair double-strand breaks (DSBs).
101
What happens to histones during cell division?
They condense to form chromosomes.
102
What are the first steps in the DNA damage response?
Damage sensors and damage signalling.
103
What happens after signalling in the DDR pathway?
Formation of repair molecules and activation of effector pathways.
104
What are the two outcomes after checkpoint activation in DDR?
Repair or cell death.
105
What are the phases of the cell cycle?
M → G₁ → S → G₂ (24-hour cycle in humans)
106
What is the role of γH2AX in DNA repair?
γH2AX loosens chromatin structure to allow access for repair machinery.
107
What are the key steps in Non-Homologous End Joining (NHEJ)?
1. MRN caps damage
2. Kinase signals repair
3. DNA ends are cut and rejoined (“sandwiched”)
108
What is a risk of NHEJ?
Loss of genetic information — it’s quick but error-prone.
109
What are the steps in Homologous Recombination Repair (HRR)?
1–2. Same start as NHEJ
3. Break is matched to healthy template
4. Template copied
5. Resolved with or without crossover
110
When is HRR used instead of NHEJ?
During the S or G₂ phase, when a sister chromatid is available.
111
What are exons?
Coding regions with no physiological relevance if mutated in this context.
112
What are introns?
Non-coding regions with physiological relevance ( likely biological effect when damaged).
113
What is the only signature of radiation-induced DSB damage?
Chromosomal aberrations.
114
Give two examples of chromosomal aberrations.
Translocations and interstitial deletions.
115
What does it mean if a cell with chromosomal aberrations enters mitosis?
It may die due to incorrect reproduction.
116
Why must the cell be dead to image chromosomal aberrations?
Because imaging methods typically require fixation and staining, which kill the cell.
117
What does in vitro mean?
In a controlled environment (e.g., test tube or petri dish).
118
What does in vivo mean?
Inside a living organism.
119
What are adaptive responses to radiation?
Cells improve at DNA repair after low-level exposure, which can make retreatment less effective.
120
What are clastogenic factors?
Biomarkers in blood that indicate possible radiation damage.
121
What does a clonogenic assay measure?
A single cell’s ability to form a colony — aka reproductive integrity.
122
What happens to 'infertile' cancer cells in a clonogenic assay?
They’re considered inactive — they can’t form colonies.
123
What kind of cells can be tested with a clonogenic assay?
Adherent cells (ones that stick to surfaces like plastic).
124
What is the formula for survival fraction (SF)?
Where:
N_t = colonies formed
N_s = cells seeded
PE = plating efficiency
125
Why is D_0 a limited metric?
It assumes a single-hit model and doesn’t capture full biological complexity — especially poor at low LET.
126
What does the Multi-Target, Single-Hit model assume?
Cells have multiple critical targets; hitting any one can be lethal.
127
What is the survival equation in the Multi-Target, Single-Hit model?
S = 1 - e^{-D/D_0}
## Footnote
(For one target)
S = 1 - e^{-nD/D_0}
## Footnote
(For n targets per cell)
128
When is the Multi-Target, Single-Hit model valid?
At high doses and with low LET radiation.
129
What’s the key idea in Multi-Target, Multi-Hit?
Damage requires multiple hits to multiple targets before cell death occurs.
130
What is the extrapolation number n?
It estimates how many hits are needed — obtained by extending the linear region of the survival curve.
131
What does the LQ model account for?
Both single lethal events (linear) and combined sub-lethal events (quadratic).
132
What is the LQ model survival equation?
S = e^{-alpha D - eta D^2}
133
What happens at low doses in the LQ model?
Linear term dominates — reflects biological sensitivity.
134
What happens at high doses in the LQ model?
Quadratic term dominates — due to multiple interactions.
135
What is D_q?
Quasi-threshold dose — the point where the curve deviates from linearity.
136
Which is more damaging: single or split doses?
Single doses — split doses allow time for DNA repair.
137
Why are split doses less effective?
They allow repair of sublethal damage, especially SSBs.
138
What is mitotic catastrophe?
Cell enters mitosis with lethal damage — usually due to ionising radiation.
139
What is apoptosis?
Programmed cell death triggered when DNA repair fails.
140
What are the 3 apoptosis pathways?
Intrinsic, extrinsic, and ceramide.
141
What are key features of apoptosis?
Blebbing,
loss of membrane integrity,
biochemical signals.
142
How is radiosensitivity related to apoptosis?
Higher radiosensitivity increases likelihood of apoptosis.
143
List 4 factors affecting type of cell death:
1. Cell type
2. Cell cycle phase during exposure
3. LET, dose, fractionation, dose rate
4. Oxygenation
144
Why are tumours often hypoxic?
Poor vasculature and necrotic cores reduce oxygen flow.
145
What happens to capillaries in tumours?
Pressure from necrotic tissue collapses them, reducing oxygen delivery.
146
What is reoxygenation?
Process where previously hypoxic tumour areas gain oxygen between treatment fractions.
147
Why is reoxygenation clinically useful?
It improves treatment effectiveness by increasing radiosensitivity.
148
What is prodromal radiation syndrome?
Early symptoms after radiation exposure.
149
What determines the severity of prodromal symptoms?
Radiation dose.
150
Does the prodromal phase resolve?
Yes, but it’s followed by more serious effects.
151
What are dose thresholds for prodromal syndrome outcomes?
1–4 Gy: recoverable; ≥5 Gy: potentially lethal.
152
What is carcinogenesis?
The initiation of cancer formation.
153
When does radiation-induced leukemia peak?
Around 10 years post-exposure.
154
How do solid cancers behave post-radiation?
No peak — risk increases linearly with time.
155
Does radiation exposure change the type of hereditary disease?
No — it only increases the likelihood of existing types.
156
What are Mendelian hereditary effects?
Single-gene mutations (autosomal dominant, recessive, or X-linked).
157
What are chromosomal hereditary effects?
Large-scale changes in chromosome number or structure.
158
What are multifactorial hereditary effects?
Involve multiple genes and environmental factors — complex inheritance.
159
How is hereditary radiation risk estimated?
By observing incidence rates in populations.
160
What is teratogenesis?
A set of radiation-induced effects seen in the fetus.
161
What are possible outcomes of teratogenesis?
Lethality, malformations, and developmental retardation.
162
What is G₂ block?
Accumulation of cells in G₂ phase during treatment, making them more sensitive to radiation.
163
How can G₂ block be exploited in therapy?
Extra dose can be timed to hit cells when they’re in the radiosensitive G₂ phase.
164
What is the inverse dose rate effect?
Lower dose rate increases G₂ block, making cells more vulnerable.
165
Why is a 6-hour gap between fractions often used?
It allows time for cell cycle redistribution, enhancing the effect of the second fraction.
166
How do tumour cells compare to healthy cells in terms of cycling?
Tumour cells accumulate more in the G₂ block because of their less reliable cycling They also surpass checkpoints more.
167
What are structurally defined functional subunits?
Subunits where cells cannot migrate between areas — damage is contained.
168
What are structurally undefined functional subunits?
Subunits where cells (or damage) can migrate between areas — effects may spread.
