Exam 1 Flashcards
calculation of Dq
quasi threshold dose
a large Dq can more easily cover than a cell with low Dq
the dose at which the straight portion of the cell survival curve extrapolated backward cut the dose axis drawn through a surviving fraction of one
If Do= D1
n will equal 0
variations in radiation sensitivities
low let RT shows a wide range of sensitivity these differences are reduced when it comes to Hi-Let radiation. This difference is due to the size of the shoulder
Intrinsic cell radio sensitivity
increasing Do indicates more resistant cells
cells from tumors have a broad range of radiosensitivities
Cell classifications
Vegetative inter-mitotic
differentiating inter mitotic
reverting post mitotic
fixed post mitotic
vegetative inter mitotic
produce cells like themselves, go through mitosis regularly
differentiating inter mitotic
divide regularly, some differentiation
reverting post mitotic
dont divide regularly, but can if needed
fixed post mitotic
do not divide, highly differentiated
plating efficiency (PE)
percentage of untreated seeded cells that grow into a colony
PE= (number of colonies)/(number of cells plated) x 100
Survival fraction (SF)
Fraction of cells surviving a given dose is determined by counting macroscopic colonies and allowing for plating efficiency
SF = (colonies survived from radiation)/ (total cells initially seeded x (PE/100))
High LET cell survival curves
Straight on semi-log plot
Low LET cell survival curves
have slope, shoulder and subsequent straight region
Linear quadratic relationship
S= e^(aD+bD^2)
a= initial slope
b= quadratic component
ratio of a/b is dose at which linear and quadratic components are equal
Cell mitotic death
majority of tumor cells have mitotic death as dominant feature, thus follows linear-guadratic model
Apoptic death
if apoptosis dominates, cells are radiosensitive if absence radio resistant
Cell death
for cells in G0 it is the loss of function
for cells in M it is the loss of capacity to divide
in context of radiobiology
if a cell losses its capacity to divide indefinitely and cant produce a colony it is considered dead
types of cell deaths
apoptosis
mitotic death
autophagy
senescence
cause cell to lose ability to proliferate indefinitely
apoptotic death (programmed cell death
radiosensitive
lymphoid cells
majority of cells NO apoptosis upon radiation
Mitotic death (passive)
most common form of cell death from radiation exposure
death due to damaged chromosomes
how to measure RT induced cell death
- In Vitro
- In Vivo (in situ)
- in Vivo ( ex situ or ex vivo)
In Vitro
COLOGENIC ASSAY
trypan blue exclusion assay
In Vivo (In Situ)
skin (pig skin) intestinal crypt cells, testes kidney tubules
In Vivo (ex situ or ex vivo)
SPLEEN COLONY ASSAY
tumor transplant
Cologenic Assay
tissue culture techniques- specimen taken from organism chopped into small pieces single cell suspension prepared by use of enzyme trypsin cell plated onto culture dish
Increasing LET survival curves
increases slope of survival curve
results in more linear curve
shoulder disappears due to increase of killing by single events
Relevant doses
100gy - destroys cell function in non-proliferating systems (nerve, muscle cells)
2gy mean lethal dose for loss of proliferative capacity (blood)
features of survival curve
low doses -shoulder
intermediate doses- region where survival curve bends and survival shows greater change with increasing dose
high dose- region where survival falls rapidly with dose
general survival models
multi target model- based on hitting the target
linear-quadratic model- dual radiation actions
1- cell killing is proportional to dose
2. cell killing is proportional to square of dose
factors regulate therapeutic ratio
- TUMOR SIZE
- DOSE RATE EFFECT
- TIME INTERVAL
- LET of radiation
- PResence of radio-sentizers/ protectors
- Plan design and precision of implementation
cell cycle resistant stages
S phase most resistant
G2 and M most sensitive
4 r’s
- REPAIR
- REDISTRIBUTION
- REPOPULATION
- REOXYGENATION
- radiosensitivity
operational classification of radiation damage
- lethal damage
- potentially lethal damage
- sublethal damage
lethal damage
irreversible, irreparable
potentially lethal damage
modified by post irradiation environment conditions
sublethal damage
can be repaired under normal circumstances
types of dna damage
abasic site base damage bulky base damage single strand break double strand break interstrand cross-link
types of simple repair
chemical repair
direct reversal of damage
1. photolyase- revert UV induced pyrimidine dimers by using visible light
2. methyl transferase- removes methyl group from damage base and adds it to itself
excision repair
base excision repair
nucleotide excision repair
mismatch repair
base excision repair
DNA glycosylase cuts out damage base- dna polymearse fills the gap. (single nucleotide cut out)
nucleotide excision repair
large strand removed and replaced
mismatch repair
proofreading of replication endunuclease makes a cut in the newly synthsized strand
Repair of DNA strand breaks
A. DNA single strand break repair
B. DNA double strand break repair
DNA single strand repair
exonuclease extends the gap- DNA poylmerase fills in the gap- dna ligase seals the strands- part of the base excision repair machinery
DNA double strand break repair
- non-homologous end joining- error prone
2. homologous recombination repair - error free
Lack of DNA repair
mutagenesis
chromosome aberrations
microsatellite
cell death
mutagenesis
if DNA damage not repaired before S-phase - DNA polymerase may put in wrong base mutations: silent, frameshift, deletions
chromosome aberrations
IR; errors in repair most chemicals: complications during replication of damaged template
microsatellite instability
loss of mismatch repair- slippage errors during replication
cell death
if cell is not able to resolve blocked transcription or blocked replication cell death- premature aging apoptosis autophagy necrosis mitotic catastrophy
carcinogenesis
initiation-> promotion-> transformation-> progression
genes involved in carcinogenesis
proto-oncogenes-> oncogenes
tumor suppressor genes (gatekeepers)(p53,Rb)
DNA stability genes(caretakers)
autophagy
genetically controlled, formation of double membrane casuoles in cytoplasm sequestering mitochondria and ribosomes
apoptosis
suicide, genetically controlled, executed by caspases and nucleases, cell shrinkage, dna degradation
necrosis
‘murder’ passively occurring, cell swelling
mitotic castastrophy
caused by mis-segregation of chromosomes, often form “micronuclei’, ‘giant’ cells or multinucleate cells, could induce apoptosis
spurs
<100eV
blob
100-500eV
short track
<5000eV
branch track
> 5000eV
direct action of radiation
radiation absorbed directly by the target
indirect action of radiation
radiation energy absorb in non-target molecule that then becomes reactive and attacks the target
the hydroxyl radical
one unpaired electron uncharged very reactive can damage dna if formed close to dna molecule major contributor to indirect IR
radical scavengers
give up electorns to radicals
can also donate hydrogens to radicals leading to chemical repair
