Cell Survival Curves

Abish Adhikari,
Resident, Radiation/Oncology
NAMS, Kathmandu
Defination
describes the relationship between
the radiation dose and the proportion
of cells that survive.
Death could be either Reproductive Death or
Functional Death
~100Gy is needed to Destroy the cell, but
only ~2Gy to functionally kill the cell.

Survival
The capability of a cell to divide and form a
colony is the sure sign of survival.
Tissue chopped Trypsin
Single cell suspension Electronic Counter
Cultivation Incubation Colonies Counting
Some Formulae
Some Formulae
Shape of the Curve
Shape of the Curve

Survival Curve
Dose plotted on a linear scale and surviving
fraction on a logarithmic scale.
At High LETs, such as -particles or low-energy
neutrons, the curve is a straight line.
For sparsely ionizing (low LET) radiations, such
as x-rays -
Survival Curve
Starts out straight with a finite initial slope;
that is, the surviving fraction is an exponential
function of dose.
At higher doses, the curve bends.
At very high doses, the survival curve often
tends to straighten again; the surviving
fraction returns to being an exponential
function of dose.
Models of Description of the Curve
Single-target Model
Multi-target Model
Linear Quadratics Model
Multi-Target Model
Described in terms of an initial slope, D
1
,
resulting from single-event killing;
A final slope, D
0
, resulting from multiple-event
killing;
And some quantity (either n or D
q
) to
represent the size or width of the shoulder of
the curve.
Multi Target Model
The quantities D
1
and D
0
are the reciprocals of
the initial and final slopes.
It is the dose required to reduce the fraction
of surviving cells to 37% of its previous value.
1 to 0.37 (i.e. to e
-1
)
For oxygenated mammalian cells, D
0
is about
150 rads (1.5 Gy).
D
q
defined as the dose at which the straight
portion of the survival curve, extrapolated
backward, cuts the dose axis drawn through a
survival fraction of unity.
three parameters,
n, D
0
, and D
q
, are
related by the
expression
log
e
n = D
q
/D
0

Linear-Quadratic Model
assumes that there are two components to
cell killing by radiation,
one that is proportional to dose (Linear)
one that is proportional to the square of
the dose. (Quadratic)
many chromosome aberrations are result of
two separate breaks. Most of them lethal.
Linear Quadratic Curve
The bendiness is determined by / ratio
S = e
-D-D2

S is the fraction of cells surviving a dose D,
and are constants.
If at a dose D, D = D
2
then: D = /
SF = e
-(D+D2)

D is the dose in Gy,
is the cell kill per Gy of the initial linear
component (on a log-linear plot) and
the cell kill per Gy
2
of the quadratic
component of the survival curve.
Survival curve for HeLa cells in culture exposed to x-rays.
Characteristically, this cell line has a small initial shoulder
Bystander Effect
Defined: the induction of biologic effects
in cells that are not directly traversed by
a charged particle, but are in close proximity
to cells that are.
~30% of bystander cells can be killed in this
situation.
Presumably due to cytotoxic molecules
released into the medium.
Apoptotic and Mitotic Death
Greek word meaning falling off, as in petals
from flowers or leaves from trees.
First, apoptosis after radiation seems
commonly to be a p53-dependent process.
Mitotic death is common: Cells die attempting
to divide because of damaged chromosomes.
S=e
-(
M
+
A
)D-
M
D2

S is the fraction of cells surviving a dose D,

M
and
A
describe the contributions to cell
killing from mitotic and apoptotic death that
are linear functions of dose,

M
describes the contribution to mitotic
death that varies with the square of the dose.

Extra-Radiosensitive
Ataxia telangiectasia (AT)
Basal cell nevoid syndrome
Cockayne's syndrome
Down's syndrome
Fanconi's anemia
Gardner's syndrome
Nijmegan breakage syndrome
Usher's syndrome
EFFECTIVE SURVIVAL CURVE FOR A
MULTIFRACTION REGIMEN
Multifraction regimens are used most often.
If a radiation dose is delivered in a series of
equal fractions, separated by sufficient time
for repair of sublethal damage to occur
between doses, the effective dose-survival
curve becomes an exponential function
of dose. thus making a straight line.
The biological effect (E) per fraction (n) of
fractional dose (D) can be expressed as:
E
n
= (D+D
2
)
So, Biologically Effective Dose
BED = E/ = nD (1 + (D / (/)))
For calculation purposes, it is often useful to
use the D
10
, the dose required to kill 90% of
the population. For example:
D
10
= 2.3 D
0
in which 2.3 is the natural logarithm of 10.
Radiation & Micro-organisms
A, mammalian cells;
B, E. coli;
C, E. coli B/r;
D, yeast;
E, phage staph E;
F, B. megatherium;
G, potato virus;
H, Micrococcus
radiodurans.

if radiation is used as a
method of
sterilization, 20,000 Gy
necessary.