Cell survival and Radiosensitivity Flashcards
Cell death
loss of function of cells that do not proliferate otherwise or reproductive death for proliferating cells
clonogenic cell
able to proliferate indefinitely and form a large colony from a single cell
the formula for plating efficiency
colonies observed/number of cells plated
surviving fraction
colonies counted/cells seeded*PE
D0 dose
a dose that introduces an avg dose for one lethal event per cell leaves 37% still viable
ED50
The dose that reduces cell survival to 50%, if repeated reduce survival to 25% and etch
Cell killing follows the exponential relationship
True and SF never reaches 0.
Effect = 𝛼D
D/D0, D0 = 1/𝛼. Slope 1/D0
SF formula
SF= exp (-D/D0)= exp (-𝛼D). When D = D0, SF = exp (-1) = 0.37
Linear-Quadratic Model
Dual radiation action
First component – cell killing is proportional to dose
Second component – cell killing is proportional to (dose)2
Multi-Target Model
Based on the probability of hitting the “target”
2 Component Model formula
S = S1 (single event killing)*S2 (two-event killing)= exp(−(αD+βD^2))
Multi Target Model Assumptions:
the cell contains n targets;
each target inactivated by one hit;
inactivation of one target is a sublethal event;
to kill the cell all targets must be hit;
on average there are one hit per target for a dose D0, S=exp(-D/D0)
Significance of the Shoulder
with low LET radiation cell can withstand higher doses if given after some time after conditioning dose. At hight LET no effect of the shoulder.
DNA as a target cell killing
Cells are killed by radioactive tritiated thymidine incorporated into the DNA. The radiation dose results from short-range alpha particles and is therefore very
localized.
Apoptotic Death
programmed cell death, characterized by a stereotyped sequence of morphologic events. Dying cell rounds up and detaches from its neighbors.
Chromatin condensation, nucleus fragmentation àcell shrinkage
Cross-linking of proteins and loss of water
Mitotic Death (necrosis
Cells die attempting to divide because of damaged chromosomes
Autophagic Cell Death
Self-digestive process that uses lysosomal degradation or long-lived proteins and
organelles to restore or maintain cellular homeostasis
Senescence
Programmed cellular stress response – unique response to accumulation of
damage to a cell
cell survival curve
the relationship between the fraction of
cells retaining their reproductive integrity and the absorbed
dose
High LET radiation
alpha particles and low-energy neutrons
