Intro to radiobiology Flashcards
How can DNA damage be caused?
Direct (ionising energy breaks DNA)
Indirect (ionising energy breaks molecule, and the resulting toxic agent breaks DNA)
What percentage of DNA damage is indirect?
Why?
85%
Most of the cell is water, not DNA
How is indirect DNA damaged caused with water?
Ionisation of water produces free radicals
Free radicals interact with DNA
Resulting radox reactions break DNA
How is indirect DNA damage caused with oxygen?
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
What are the main types of DNA damage, and how damaging are they?
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
What are deterministic effects?
What are some examples?
What damage are they caused by?
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
What are stochastic effects?
What are some examples?
What damage are they caused by?
Probability increases with dose
eg. carcinogenesis, birth defects in future children
Caused by:
Viable alteration
Mutation
Change in function/behaviour
Do cells all spend the same amount of time in each phase?
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
What does DNA damage repair capability depend on?
Cell type
What phase the cell is in
What does failure of a cell to repair lead to?
Cell death
Reproductive death (if in G0)
Mutation
Does radiosensitivity increase or decrease with increased mitotic activity?
Increase
Does radiosensitivity increase or decrease with increased differentiation?
Decrease
The law of Bergonie and Tribondeau says that ionising radiation is more effective against cells that…
Are actively mitotic
Are undifferentiated
Have a long mitotic future
What are some characteristics of radiosensitive cells?
High mitotic rate
Poorly differentiated
Late G2 or M phase
What are some characteristics of radioresistant cells?
Low mitotic rate
Well differentiated
G1 or early S phase
Why does is a high mitotic rate a characteristic of radiosensitive cells?
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
How does oxygen affect radiosensitivity?
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
What are radiosensitisers?
Chemicals that can make the cell environment more conducive to radiation damage
What is a cell survival curve?
A count of the surviving fraction of cells following irradiation at discrete intervals of dose
What shape is a cell survival curve?
Exponential decay
The survival drops from 100% as dose increases
What can be done to the y axis of cell survival curves to make it easier to see that difference between them?
Take the log
What factors affect cell survival?
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
What causes a decrease in the curved shoulder of a cell cycle curve?
Increase in energy transfer rate
Increase in radiosensitivity
What effect does increased LET rate have on a cell survival curve?
A decrease in the curve shoulder
What effect does increased radiosensitivity have on a cell survival curve?
A decrease in the curve shoulder
