3. Tissue Response to Radiation Flashcards by J Y

what are the 3 natures of radiation induced DNA damage

hydrogen bond break
molecular degradation
cross linking

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what is DNA base damage

one is damaged and doesnt bind to the neighbouring molecule

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what are the 7 forms of DNA damage

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

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

base excision repair

nucleotide exicsion repair

homologous recombination repair

non-homogolous end joining

apoptosis

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what are the 4 steps of base excision repair

damaged base identified and removed

cleaves sugar phosphate backbone

replace missing base

join strand segments

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

yes

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

no other mechanisms needed

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

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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what does HRR do in terms of genetic integrity

preserves it

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

NHEJ more common and faster and leads to more errors

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what is the process of NHEJ and HRR

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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which is more error prone HRR or NHEJ

which is more complex

NHEJ = more errors

HRR = more complex process

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what are the 2 types of lethal chromosomal aberrations

dicentric and ring aberrations

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why are some chromosomal aberrations lethal

disrupts mitosis and can lead to cell death

mitosis disrupted owing to chromosome aberration

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what is dicentric aberrations

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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what is ring aberrations

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

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why are some chromosomal aberrations nonlethal

despite not being lethal what is a major long term problem

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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what are the 4 checkpoints for a DNA chromosome

G0
G1/S
G2/M
M

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what is are the 4 DNA chromosome checkpoints for

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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where is the G1 check point and what does it do

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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where is the G2 check point and what does it do

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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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

no damage = cell continues to function normally

damage = lethal or potentially repairable

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

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reproductive death so cell dies

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

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repair error or correct repair

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

cell dies or there is a mutation | mutation could be lethal so cell dies or viable so cell passes mutation to future generations

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

cell continues to function normally

what are the 4 steps of calculating cell survival

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

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

seed a number of cell colonies incubate for desired time with no radiation present count surviving colonies

what is the plating effciency equation

PE = # of colonies counted/# of colonies seeded

what is the surviving fraction equation

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

what does it mean when you calculate the cell survival

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

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

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

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

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

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

decreases

for a cell survival fraction graph what is the scale

logarithmic going up by factors of 10

what are the 3 models for the cell survival curve

exponential response model linear-quadratic multi target model

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

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 ```

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

measure of slope higher Do = much sharper decline

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

Do = 1/slope measure of how radiosensitive a cell population is

what is 'n' in the multi target model of cell survival what does it measure

extrapolation of the linear portion measures the size of the shoulder

what is the Dq in the multi target model of cell survival what does it measure

width of the shoulder region measures sublethal damage

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

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

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

Survival fraction of 1 the intersection with other line the width

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

linear portion of graph line individual particle tracks independent of dose rate

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

quadratic portion of the graphline 2 or more particle tracks depends on the dose rate

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

beta

what does alpha/beta represent in the linear quadratic model of cell survival what is it a measure of

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

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

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

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

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

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

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

what is the LET

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

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

no shoulder at all as all of the damage is lethal

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

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

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

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

what is the effect of fractionation on the cell survival curve why

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

3. Tissue Response to Radiation Flashcards

(55 cards)