Cell Survival Curve 120126084118 Phpapp01

8/11/2019 Cell Survival Curve 120126084118 Phpapp01

1/33

Cell Survival Curves

Abish Adhikari,

Resident, Radiation/OncologyNAMS, Kathmandu


2/33

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.


3/33

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


4/33


5/33

Some Formulae


6/33


7/33

Some Formulae


8/33


9/33

Shape of the Curve


10/33

Shape of the Curve


11/33

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 -


12/33

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.


13/33


14/33

Models of Description of the Curve

Single-target Model

Multi-target Model

Linear Quadratics Model


15/33

Multi-Target Model

Described in terms of an initial slope, D1,

resulting from single-event killing;

A final slope, D0

, resulting from multiple-event

killing;

And some quantity (either n or Dq) to

represent the size or width of the shoulder of

the curve.


16/33

Multi Target Model

The quantities D1and D0are the reciprocals ofthe initial and final slopes.

It is the dose required to reduce the fractionof surviving cells to 37% of its previous value.

1 to 0.37 (i.e. to e-1)

For oxygenated mammalian cells, D0is about150 rads (1.5 Gy).

Dqdefined as the dose at which the straightportion of the survival curve, extrapolatedbackward, cuts the dose axis drawn through asurvival fraction of unity.


17/33

three parameters,

n, D0, and Dq, are

related by theexpression

logen = Dq/D0


18/33

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)


19/33

many chromosome aberrations are result of

two separate breaks. Most of them lethal.


20/33

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= D2then: D = /


21/33


22/33


23/33

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 Gy2of the quadratic

component of the survival curve.


24/33

Survival curve for HeLa cells in culture exposed to x-rays.

Characteristically, this cell line has a small initial shoulder


25/33

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.


26/33

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.


27/33

S=e-(M+

A)D-

MD2

S is the fraction of cells surviving a dose D,

Mand Adescribe the contributions to cell

killing from mitotic and apoptotic death that

are linear functions of dose,

Mdescribes the contribution to mitotic

death that varies with the square of the dose.


28/33

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


29/33

EFFECTIVE SURVIVAL CURVE FOR A

MULTIFRACTION REGIMEN

Multifraction regimens are used most often.

If aradiation 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.


30/33


31/33

The biological effect (E) per fraction (n) of

fractional dose (D) can be expressed as:

En= (D+D2

) So, Biologically Effective Dose

BED = E/ = nD (1 + (D / (/)))


32/33

For calculation purposes, it is often useful to

use the D10, the dose required to kill 90% of

the population. For example:

D10= 2.3 D0in which 2.3 is the natural logarithm of 10.


33/33

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

Documents

Cell Survival Curve 120126084118 Phpapp01