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202 MEDIMAGE > 3. Tissue Response to Radiation > Flashcards

3. Tissue Response to Radiation Flashcards

1
Q

what are the 3 natures of radiation induced DNA damage

A

hydrogen bond break
molecular degradation
cross linking

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2
Q

what is DNA base damage

A

one is damaged and doesnt bind to the neighbouring molecule

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3
Q

what are the 7 forms of DNA damage

A 
base damage
base deletion
base substitution
Hydrogen bond disruption
single strand break
double strand break
complex damage
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4
Q

what are the 5 ways DNA repair can occur after radiation induced damage

A

base excision repair

nucleotide exicsion repair

homologous recombination repair

non-homogolous end joining

apoptosis

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5
Q

what are the 4 steps of base excision repair

A

damaged base identified and removed

cleaves sugar phosphate backbone

replace missing base

join strand segments

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6
Q

after base excision repair is the DNA still the same form and info as it was beofre

A

yes

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7
Q

can base excision repair be used to repair DNA if complex damage has occured (eg multiple base pairs, strands damage)

A

no other mechanisms needed

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8
Q

what is the difference between homologous recombination repair and non-homologous end joining

A

homo recomb uses homologous DNA strands for repair

non homo end joining uses end to end joining of broken ends

HRR involving exchanges with homologous DNA strands (from sister chromatids after replication or from homologous chromosomes).

NHEJ involves end-to-end joining of broken strands

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9
Q

what does HRR do in terms of genetic integrity

A

preserves it

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10
Q

which is more common HRR or NHEJ and which is faster and which is more erroneous

A

NHEJ more common and faster and leads to more errors

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11
Q

what is the process of NHEJ and HRR

A

identify where ends are and process them to make sure they are able to be recombined and synthesise info along the strands

join damaged ends (HRR replace with same info, NHEJ not replaced with same info as before)

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12
Q

which is more error prone HRR or NHEJ

which is more complex

A

NHEJ = more errors

HRR = more complex process

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13
Q

what are the 2 types of lethal chromosomal aberrations

A

dicentric and ring aberrations

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14
Q

why are some chromosomal aberrations lethal

A

disrupts mitosis and can lead to cell death

mitosis disrupted owing to chromosome aberration

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15
Q

what is dicentric aberrations

A

2 chromosomes cleaved at similar places and recombine with 2 contromere on chromosome or one without a centromere (acentric fragment) so cant go through mitosis normally

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16
Q

what is ring aberrations

A

acentric fragment left but dont have structure that can be passed on to go through effective mitosis and cell replication

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17
Q

why are some chromosomal aberrations nonlethal

despite not being lethal what is a major long term problem

A

single intact centromere allows mitosis to proceed.

but errors can be passed down through generations of cells as genetic info is different in each set of chromosomes but still suitable for mitosis to proceed

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18
Q

what are the 4 checkpoints for a DNA chromosome

A

G0
G1/S
G2/M
M

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19
Q

what is are the 4 DNA chromosome checkpoints for

A

checks integrity of DNA chromosome so it can progress to the next stage of cell formation or initiate apoptosis if integrity has been compromised

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20
Q

where is the G1 check point and what does it do

A

at the end of G1 stage pre DNA synthesis/before S stage of interphase

pre DNA synthesis and check integrity of DNA

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21
Q

where is the G2 check point and what does it do

A

in the G2 phase of interphase post DNA synthesis and pre mitosis

checks DNA synthesis has gone normally and is completed before mitosis is triggered

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22
Q

what are the possibilities for the cell to go through if there is no DNA damage

what if there is damage what are the 2 routes

A

no damage = cell continues to function normally

damage = lethal or potentially repairable

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23
Q

what are the possibilities for the cell to go through if there is lethal DNA damage

A

reproductive death so cell dies

24
Q

what are the 2 possibilities for the cell to go through if there is potentially repairable DNA damage

A

repair error or correct repair

25
Q

what are the possibilities for the cell to go through if there is potentially repairable DNA damage and it goes through the repair error route

A

cell dies or there is a mutation

mutation could be lethal so cell dies or viable so cell passes mutation to future generations

26
Q

what are the possibilities for the cell to go through if there is potentially repairable DNA damage and it goes through the correct repair route

A

cell continues to function normally

27
Q

what are the 4 steps of calculating cell survival

A

perform a survival assay on a cell culture

repeat survival assay on genetically identical cell cultures

repeat for various radiation doses

plot the SF at each dose on a graph

28
Q

what are the 3 steps for performing a survival assay when calculating cell survival

A

seed a number of cell colonies

incubate for desired time with no radiation present

count surviving colonies

29
Q

what is the plating effciency equation

A

PE = # of colonies counted/# of colonies seeded

30
Q

what is the surviving fraction equation

A

SF = # of colonies counted/(# of colonies seeded x PE)

31
Q

what does it mean when you calculate the cell survival

A

investigating if a group of cells are exposed to radiation how does it affect the overall survival of cells

want to find the cell survival at different doses

32
Q

what is the purpose of calculating the plating efficiency when calculating the cell survival

A

seed a number of colonies and incubate for a period of time without excess radiation and find the survival of this population

count how many cell colonies remain (PE) to see what the expected survival time is in that cell population

33
Q

what is the purpose of calculating the surviving fraction when calculating the cell survival

A

incubate and now exposed to radiation

count surviving colonies to find the SF

multiply with PE as a measure of how many would have survived at that point anyways

34
Q

in a cell survival fraction graphs as the dose increases what happens to the number of cells surviving

A

decreases

35
Q

for a cell survival fraction graph what is the scale

A

logarithmic

going up by factors of 10

36
Q

what are the 3 models for the cell survival curve

A

exponential response model

linear-quadratic

multi target model

37
Q

what is the survival fraction equation for the exponential cell survival curve

A

SF = N/No = e^(-D/Do)

N = total number of cells measured along that curve
No = number of cells started with 
Do = dose that reduces the number of cells to 37% of the initial number
38
Q

in the exponential cell survival curve what is the Do a measure of and what does a high Do show on the graph

A

measure of slope

higher Do = much sharper decline

39
Q

what is the relationship between Do and the slope in the multi target model of cell survival

what is Do a measure of

A

Do = 1/slope

measure of how radiosensitive a cell population is

40
Q

what is ‘n’ in the multi target model of cell survival

what does it measure

A

extrapolation of the linear portion

measures the size of the shoulder

41
Q

what is the Dq in the multi target model of cell survival

what does it measure

A

width of the shoulder region

measures sublethal damage

42
Q

in the curved portion and the shoulder width of the multi target model of cell survival what does it represent in terms of cell recovert

A

cell is likely to recover

not all the cell pop is going to die, some will recover

shoulder width indicates more than one hit of the cell may be recoverable

43
Q

which aspects of the graph line in the multitarget model of cell survival indicates the sublethal damage

A

Survival fraction of 1 the intersection with other line the width

44
Q

in the linear quadratic model of cell survival what does alpha represent

in terms of which portion of the graph line, what it actually represents

is it independent or dependent on the dose rate

A

linear portion of graph line

individual particle tracks
independent of dose rate

45
Q

in the linear quadratic model of cell survival what does the beta stand for

in terms of which portion of the graph line, what it actually represents

is it independent or dependent on the dose rate

A

quadratic portion of the graphline

2 or more particle tracks

depends on the dose rate

46
Q

in the linear quadratic model of cell survival is the alpha portion or the beta portion of the graphline dependent on the dose rate

A

beta

47
Q

what does alpha/beta represent in the linear quadratic model of cell survival

what is it a measure of

A

dose where alpha = beta

where the amount of dose causing cell death is about the same as recoverable, ratio lower in pop that does more lethal radiation

measure of radio sensitivity

48
Q

what is the equation for survival fraction for the linear quadratic model of cell survival

A

SF(D) = e^(-aD + BD^2)

49
Q

which portion in the linear quadratic model of cell survival represents cell death and recovery? in terms of alpha and beta

A

linear alpha portion is high LET radiation so more likely to deposit energy and more cell death

Beta Quadratic portion is low LET radiation, more recoverable, may damage certain parts of DNA that can be repaired reasonably we

50
Q

what does a long shoulder portion mean in the linear quadratic model of cell survival

A

indicates it takes higher and higher doses to get significant cell death

51
Q

what is the LET

A

linear energy transfer (LET) is the amount of energy that an ionizing particle transfers to the material traversed per unit distance

52
Q

in the linear quadratic model of cell survival is there a shoulder portion for alpha particles

why

A

no shoulder at all as all of the damage is lethal

53
Q

what is the effect of dose rate on the cell survival curve

a low dose rate and high dose rate results in what for the curve

A

low dose means not bombarding with radiation the whole time so has a chance to recover (shoulder broad as damage is recoverable until you get to much higher doses)

High doses = more lethal damage much earlier on so less shoulder

54
Q

what is the effect of Presence of O2 (environment where cells exist) on the cell survival curve

why

A

higher O2 presence decreases shoulder width
(hypoxic environment has wider shoulder on curve)

When there’s free radicals O2 has to stabilize them which increases probability that the free radicals will combine with nearby substances

O2 stabilizes free radicals and allows more damage in tissues so lethal damage

More free radicals = more damage, O2 stabilizes free radicals and can potentially do more damage as free radicals hang around longer

55
Q

what is the effect of fractionation on the cell survival curve

why

A

fractionation is how cells react to radiation

One big dose of rad therapy to tissue, lots of cell death if it’s a high dose, fractionation is where you apply small doses at certain intervals

Total curve a lot shallower so gives healthy tissue time to recover where if you applied it at once they wont have time to recover

202 MEDIMAGE (18 decks)

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