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Principles of radiobiology for FRCR CO1 > 1.6 Principles of radiobiology > Flashcards

1.6 Principles of radiobiology Flashcards

1
Q

What are the 6 R’s of radiobiology?

A

Repair
Redistribution/Reassortment
Reoxygenation
Repopulation
Radiosensitivity
Remote bystander effects

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2
Q

How does Repair affect radiation damage?

A
  1. In normal tissues repair can occur so normal tissue is ultimately spared. Why fractionation is used.
  2. Repair is inefficient in malignant cells and therefore kills them
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3
Q

How is redistribution/reassortment relevant?

A

Synchronisation of the cell cycle, the radiosensitive phases are G2 -> M, much more prone to damage in these phases.

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4
Q

How is reoxygenation relevant to radiobiology?

A

Sensitivity is increased in well-oxygenated tissue due to oxygenation fixation in cell damage

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5
Q

How is repopulation relevant to radiobiology?

A

If the cell recovery rate is greater than the cell kill rate then radiation won’t destroy the population

This is good in normal tissue recovery but bad for tumour resistance

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6
Q

What is Intrinsic Radiosensitivity?

A

Some cells are more sensitive to radiotherapy - can be exploited

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7
Q

What are the Remote bystander effects?

A
  • Growth inhibition
  • Apoptotic death
  • Genomic instability
  • Cell dormancy and proliferation arrest
  • Immunogenicity - release of cell antigens which upregulate the immune system
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8
Q

What are the timescales for radiation effects?

A

Physical - seconds
Chemical - seconds to minutes
Biological - minutes to years

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9
Q

What are the physical radiation effects to the cell?

A
  • Excitations
  • Ionisations
  • Free-radical reactions
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10
Q

What are the chemical radiation effects to the cell?

A
  • Free-radical reactions
  • Enzyme reactions
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11
Q

What are the biological radiation effects to the cell?

A
  • Enzyme reactions
  • DNA repair
  • Early effects
  • Late effects
  • Carcinogenic effects
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12
Q

What are the timescales for the impacts on the cell?

A

Minutes - DNA damage
Hours - chromosome aberrations
Days - cell kill and mutations
Years - cancer

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13
Q

What do the biological effects of radiation depend on? (6)

A
  1. Total dose - cumulative effect
  2. Fraction size
  3. Dose rate
  4. Total treatment time
  5. Treated volume
  6. Dose distribution
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14
Q

What is the Linear Quadratic Model?

A

Describes cell survival curve (modelled in cells in culture not IRL)

Plots surviving cells (y) and absorbed dose (D)

Linearly this is a backwards sigmoid
Log this is a downward curve

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15
Q

What are the cellular systems?

A

Hierarchical and flexible

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16
Q

Hierarchical cell systems divide?

A

Quickly

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17
Q

What is the mean lethal dose for stem cells in hierarchical tissues?

A

<2Gy

Tissue damage is independent of dose

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18
Q

What type of responding tissue are hierarchical tissues?

A

Early

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19
Q

How do flexible tissues divide?

A

Slowly

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20
Q

What is the mean lethal dose for flexible tissues?

A

Non-proliferating cells - 100Gy

Tissue damage is dose dependent

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21
Q

What type of responding tissue is flexible tissue?

A

Late responding

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22
Q

What are parallel tissues?

A

Damage to a functional subunit of a tissue doesn’t affect the overall organ function

There is high functional reserve capacity

These tissues are sensitive to overall dose volume

e.g. lungs, liver kidneys

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23
Q

What are serial tissues?

A

Damage to one functional subunit can result in loss of function of the entire organ

Low functional reserve capacity

Sensitive to hotspots

e.g. spinal cord, oesophagus, rectum

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24
Q

What is a functional subunits?

A

Largest tissue volume that can be regenerated from a single surviving clonogenic cell without loss of the specified function

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25
Q

What is a regrowth curve?

A

Describes the regrowth of tumour cells over time after they have been partially eradicated by treatment

26
Q

What is the endpoint of a regrowth curve?

A

The time taken for the tumour to regrow to a certain volume

27
Q

What is Tumour Growth Delay?

A

Assess the efficacy of treatment in slowing tumour dose, compared to a control tumour

TGD = Ttreated - Tcontrol
T = time taken to reach specified volume

28
Q

What are clonogenic cells?

A
  • Can divide (at least 7 generations)
  • A clonogenic tumour cell would have the capacity to generate a new tumour
  • A clonogenic normal tissue cell can regenerate functional tissue
29
Q

What do clonogenic assays do?

A

Measure reproductive integrity after irradiation

30
Q

What is the Surviving Fraction? (SF)

A

Fraction of irradiated cells that maintain their reproductive integrity - ability to divide (clonogenic cells)

no. of colonies formed after treatmen/no. of cells seeded x Plating Efficiency

31
Q

What is the Plating Efficiency (PE)?

A

Proportion of irradiated cells that would actually form colonies under control conditions (growing probability)

no. of colonies formed/no. of cells seeded

32
Q

What is Linear Energy Transfer?

A

Average energy transferred by ionising radiation per unit length of track (keV/um)

High LET deposits more energy locally and is therefore more damaging

33
Q

What does LET apply to?

A

Charged particles only e.g. LET of photons is actually just the LET of the secondary electrons generated by photon interactions

Collision interactions only

34
Q

What is stopping power?

A

Energy loss per unit thickness of material - how able the material is to stop electrons

35
Q

What is the Track-averaged LET?

A

measure of the energy deposited per unit length of its path/ averaged over all the tracks of the particles passing through the medium

keV/m (energy per micrometer)

36
Q

What is the Dose-averaged LET?

A

measure of the energy deposited by radiation per unit length of its pass, averaged by the amount of dose (energy per unit mass) delivered by each particle.

37
Q

What is restricted vs. unrestricted LET?

A

Unrestricted - particles transporting energy outside patient counted
Restricted - particles transporting energy outside patient not counted

38
Q

What changes LET?

A
  1. Proportional to charge
    - Charge density of the medium
    - Charge^2 of the particle moving through the medium
  2. Inversely proportional to energy and speed
    - Energy of the particle moving through the medium
    - Speed^2 of the particle
39
Q

What type of radiation has high LET?

A

Densely ionising

1Gy would be about 4 tracks

e.g.
- alpha particles
- neutrons
- heavy ions

40
Q

What is the relative biological effectiveness of high LET radiation?

A
  • More cell killing per Gy
  • As LET increases RBE increases until >100keV (overkill)
  • RBE for high LET particles is greater for hypoxic cells
41
Q

What is the Oxygen Enhancement Ratio for high LET radiation?

A

Low

and therefore what is it for Low LET?

42
Q

What type of DNA damage to high LET radiation cause?

A
  • Direct
  • Irreversible
  • Clustered

and therefore what is it for Low LET?

43
Q

What is the a/B ratio of high LET compared to low LET?

A

a/B is higher for high LET

and therefore what is it for Low LET?

44
Q

What effect does fractionation have on high LET radiation?

A

smaller than on lower LET

45
Q

What type of particles have high LET?

A

High charge
High atomic number (z)

and therefore what is it for Low LET?

46
Q

What does high LET radiation prevent in cells?

A
  • Split dose recovery (recovery between doses)
  • Damage recovery
47
Q

What type of radiation has low LET?

A
  • Sparsely ionising
    e.g. electrons, x-rays/photons, gamma rays

Lots (1000 per Gy) of very wandering tracks through the nucleus, randomly irradiate bits of DNA

Protons start as low LET but become high LET at Bragg peal

48
Q

What is the relative biological effectiveness of low LET radiation?

A

Less cell killing per gray

RBE independent

49
Q

What is the equivalent dose?

A

D X Q (Q = radiation weighting factor Wr)

Incorporates biological effects alongside physical parameters by applying a waiting

50
Q

What is a free radical?

A

Uncharged, highly reactive, short-lived unpaired electron (.)

51
Q

What free radical causes 70% of DNA damage?

A

.OH - Hydroxyl (also H. and e-aq)

Formed by irradiation of water

52
Q

What two types of radiation interaction with DNA are there?

A
  • Direct - radiation interacts directly with DNA
  • Indirect - radiation interacts with other molecules, produces free radicals which damage DNA
53
Q

What types of DNA damage can radiation cause?

A

(number of these damages per 1Gy)

  1. DNA-protein crosslink breaking (150)
  2. SSB (1000)
  3. DSB (40)
  4. Base damage (3000)
  5. Inter and intra strand cross-links
54
Q

What type of DNA radiation damage induces cell death?

A

Double-stranded DNA

55
Q

What types of chromosomal aberrations are caused by radiation damage?

A
  1. DNA strand breaks in two different chromosomes
    - can exchange during repair to form a symmetrical translocation or lead to a deletion
  2. Lethal
  3. Non-lethal
56
Q

What are the lethal chromosomal aberrations caused by radiation?

A
  1. Dicentric chromosome
  2. Ring chromosome
  3. Anaphase bridge
57
Q

What are the non-lethal chromosomal aberrations caused by radiation?

A
  1. Small deletion
  2. Terminal deletion
  3. Symmetrical translocations
  4. MSI
58
Q

What is the relationship between absorbed dose and aberrations per cell?

A

Linear quadratic

At low doses a single radiation track can induce aberrations, at higher doses two tracks can be involved

59
Q
A
60
Q
A

Principles of radiobiology for FRCR CO1 (1 decks)

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