Intro to radiobiology Flashcards

1
Q

How can DNA damage be caused?

A

Direct (ionising energy breaks DNA)

Indirect (ionising energy breaks molecule, and the resulting toxic agent breaks DNA)

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2
Q

What percentage of DNA damage is indirect?

Why?

A

85%

Most of the cell is water, not DNA

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3
Q

How is indirect DNA damaged caused with water?

A

Ionisation of water produces free radicals
Free radicals interact with DNA
Resulting radox reactions break DNA

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4
Q

How is indirect DNA damage caused with oxygen?

A

Done by the oxygen dissolved in water (not the O in H2O)

This is not direct damage, but it ‘fixes’ the damage done to DNA by binding to the broken end, inhibiting actual repair

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5
Q

What are the main types of DNA damage, and how damaging are they?

A

Base pair injury (damage to 1 of a base pair) GENERALLY REPAIRABLE, ERROR FREE

Base pair cross-linkage (abnormal base pairing) GENERALLY REPAIRABLE, ERROR FREE

Base pair deletion (destruction of both bases in a pair MOSTLY REPAIRABLE, ERROR PRONE

Single strand break
SOMETIMES IRREPARABLE

Double strand break
GENERALLY IRREPARABLE
MAXIMUM DAMAGE

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6
Q

What are deterministic effects?
What are some examples?
What damage are they caused by?

A

They happen over a threshold dose
The severity of the effect is dose related
eg. skin reaction, hair loss

Caused by:
Repair
Reproductive delay
Reproductive death
Apoptosis
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7
Q

What are stochastic effects?
What are some examples?
What damage are they caused by?

A

Probability increases with dose
eg. carcinogenesis, birth defects in future children

Caused by:
Viable alteration
Mutation
Change in function/behaviour

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8
Q

Do cells all spend the same amount of time in each phase?

A

No
They all spend the same amount of time in M phase
BUT
They spend a different amount of time in other phases
SO
The proportion of time spent in M is different

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9
Q

What does DNA damage repair capability depend on?

A

Cell type

What phase the cell is in

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10
Q

What does failure of a cell to repair lead to?

A

Cell death
Reproductive death (if in G0)
Mutation

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11
Q

Does radiosensitivity increase or decrease with increased mitotic activity?

A

Increase

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12
Q

Does radiosensitivity increase or decrease with increased differentiation?

A

Decrease

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13
Q

The law of Bergonie and Tribondeau says that ionising radiation is more effective against cells that…

A

Are actively mitotic
Are undifferentiated
Have a long mitotic future

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14
Q

What are some characteristics of radiosensitive cells?

A

High mitotic rate
Poorly differentiated
Late G2 or M phase

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15
Q

What are some characteristics of radioresistant cells?

A

Low mitotic rate
Well differentiated
G1 or early S phase

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16
Q

Why does is a high mitotic rate a characteristic of radiosensitive cells?

A

A high mitotic rate means that a cell spends a higher proportion of time in the M phase where it is vulnerable, and less time in phases where it can perform repair

17
Q

How does oxygen affect radiosensitivity?

A

It bonds to the ends of DNA damaged by redox reactions (not by direct damage), making the damage permanent
More free radicals form in the presence of oxygen

18
Q

What are radiosensitisers?

A

Chemicals that can make the cell environment more conducive to radiation damage

19
Q

What is a cell survival curve?

A

A count of the surviving fraction of cells following irradiation at discrete intervals of dose

20
Q

What shape is a cell survival curve?

A

Exponential decay

The survival drops from 100% as dose increases

21
Q

What can be done to the y axis of cell survival curves to make it easier to see that difference between them?

A

Take the log

22
Q

What factors affect cell survival?

A
Radiation variables:
Particle size
Particle charge
Dose rate
Linear energy transfer (the greater the energy delivered per unit time as the radiation passes through the tissue, the less of a shoulder is seen)

Tissue variables:
Mitotic rate
Cell cycle phase
Oxygenation

23
Q

What causes a decrease in the curved shoulder of a cell cycle curve?

A

Increase in energy transfer rate

Increase in radiosensitivity

24
Q

What effect does increased LET rate have on a cell survival curve?

A

A decrease in the curve shoulder

25
Q

What effect does increased radiosensitivity have on a cell survival curve?

A

A decrease in the curve shoulder