cell survival curve 2

7/31/2019 Cell Survival Curve 2

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BY

DR.SALAKO

DR.AHMED,R.O


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The Cell Survival Curve shows the relationship that exists betweenthe radiation dose and the proportion of cells that survive.

All living organisms are made up of PROTOPLASM which containsorganic & inorganic substances suspended in water. The smallest unitof the protoplasm capable of independent existence is the Cell.

Cells contain inorganic substances ( water and minerals) and organiccompounds (proteins, carbohydrates, lipids and nucleic acids). The twomain constituents of a cell are the cytoplasm, which supports allmetabolic functions within the cell, and the nucleus, which containsthe genetic information (DNA).

Human cells are either somatic cells orgerm cells.Cells propagatethrough division: division of somatic cells is calledMitosis, while

division of germ cells is calledMeiosis. When a somatic cell divides,two cells are produced, each carrying a chromosome complementidentical to that of the original cell. The new cells themselves mayundergo further division, and the process continues.


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LabileCells

Quiescent/ Stable

Cells

PermanentCells

Cells proliferate throughout life,replacing those that are destroyed e.gCells that line stratified squamous

surfaces of the skin, oral cavity,vagina, and cervix.

Cells that have low levels of replication& are considered to be in the G0 stageof the cell cycle but can be stimulatedto enter G1. e.g. parenchymal cells of

liver, kidneys, and pancreas;mesenchymal cells such as fibroblasts

and smooth muscle

Cells that have left the cell cycle andcannot undergo mitotic division inpostnatal life e.g. neurons , skeletal

and cardiac muscle cells.


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the series of events in a eukaryotic cell betweenone cell division and the next.

The cell cycle consists of four distinctphases:G1phase,S phase,G2 phase (collectively known asinterphase) andM phase.

M phase is itself composed of two tightly coupledprocesses: mitosis, in which the cell'schromosomes are divided between the twodaughter cells, and cytokinesis, in which the cell'scytoplasm physically divides.


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G1 (presynthetic); S (DNA synthesis); G2 (premitotic); M (mitotic phase)

Quiescent cells are in a physiologic state called G0.


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Cell death ofnon-proliferating (static) cells isdefined as the loss of a specific function;

For stem/labile cells and other cells capable of many

divisions it is defined as the loss of reproductiveintegrity (reproductive death).

A surviving cell that maintains its reproductiveintegrity and proliferates almost indefinitely is said to

be Clonogenic.


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Classified in terms of:

Their nature e.g. Electromagnetic (X-rays and rays) or particulate(electrons,particles,neutrons, protons, pi-messons)

Linear energy transfer (LET)

Sparsely Intermediate Densely ionizing

Ionizing ionizing

Mode of production e.g. intra-or extra- nuclear production

Radiation damage to mammalian cells is divided into three categories:

Lethal Damage, which is irreversible, irreparable and leads to cell death;Sublethal Damage, which can be repaired in hours unless additional

sublethal damage is added that eventually leads to lethal damage;

Potentially Lethal Damage, which can be manipulated by repair when cells

are allowed to remain in a non-dividing state.


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A cell survival curve describes the relationshipbetween the surviving fraction of cells (i.e. the fractionof irradiated cells that maintain their reproductiveintegrity (clonogenic cells) and the absorbed dose.

Cell survival as a function of radiation dose isgraphically represented by plotting the survivingfraction on a logarithmic scale on the ordinate (y-axis)against dose on a linear scale on the abscissa(x-axis).


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First In Vitro survival curve was reported in1956withmuch excitement byPuck&Marcus.

There were a few skeptics like Dr Spearwho believed

that the In Vitro behaviour of cells would not survivethe test of time In Vivo as evidenced in an historicpublic lecture he delivered in 1957.

The few optimists like Dr David Gould, a Professor of

Radiology at the University of Colorado were howevervindicated as time passed by when techniques becameavailable In Vivo, the parameters of dose-responserelationships were shown to be quite similar In Vitro.


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Surviving Cell Fractions are plotted in a logarithmicscale on the Ordinate(y-axis) and radiation dose onthe abscissa(x-axis).

Type of Radiation influences theSHAPE

of the CSC;

-High LET (densely ionizing) radiations- straight lines

(Survival is an exponential function of the dose)

-Low LET (sparsely ionizing) -

.initially straight with a slope D1;

.followed by curvyShoulderregion and

.become straight at higher doses with another

slope D0.


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FIG. 1. Typical cell survival curves for high LET (denselyionizing) radiation and low LET (sparsely ionizing) radiation.(a) The earlier Multitarget Single Hit model; (b) The

current Linear Quadratic Model.


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Various mathematical/biophysical models have beenproposed to describe the shape of the CSC :

A.Linear Quadratic Model This is currently used todescribe the CSC. It assumes that there are twocomponents to cell kill by radiation:

S(D) = e -D-D2, S(D) = e (D+D2)

where S(D) is the fraction surviving at dose D, is theconstant that describe the initial slope, is thesmaller constant that describe the Quadraticcomponent.


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B. Multi-Target Single Hit Model- This is the earliermodel which is assumed to have a little biologicalbasis. It is described by:

D1, the initial slope which is said to be due to singleevent killing.

D0, the final slope which is due to multiple eventkilling(Both D1 & D0 are said to be the dose to reduce

fraction of surviving cells to 37% of its previous value) Dq & n are used to represent the size or width of the

shoulder.


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Dq which is called the Quasi-threshold dose is defined asthe dose at which the straight portion of the curve

extrapolatedbackwards, cuts the dose axis drawn througha survival fraction of unity.

Since there is no dose below which radiation dose does notproduce any effect( threshold dose), the Dq is the closestthing.


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cell survival curve 2

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