BY DR.SALAKO DR.AHMED,R.

 The Cell Survival Curve shows the relationship that exists between

the radiation dose and the proportion of cells that survive. All living organisms are made up of PROTOPLASM which contains organic & inorganic substances suspended in water. The smallest unit of the protoplasm capable of independent existence is the Cell. Cells contain inorganic substances ( water and minerals) and organic compounds (proteins, carbohydrates, lipids and nucleic acids). The two main constituents of a cell are the cytoplasm, which supports all metabolic functions within the cell, and the nucleus, which contains the genetic information (DNA). Human cells are either somatic cells or germ cells.Cells propagate through division: division of somatic cells is called Mitosis, while division of germ cells is called Meiosis. When a somatic cell divides, two cells are produced, each carrying a chromosome complement identical to that of the original cell. The new cells themselves may undergo further division, and the process continues.

Labile Cells

Cells proliferate throughout life, replacing those that are destroyed e.g Cells 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 stage of the cell cycle but can be stimulated to 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 and cannot undergo mitotic division in postnatal life e.g. neurons , skeletal and cardiac muscle cells.

Quiescent / Stable Cells

Permanent Cells

 the series of events in a eukaryotic cell between

one cell division and the next. The cell cycle consists of four distinct phases:G1 phase,S phase,G2 phase (collectively known as interphase) and M phase. M phase is itself composed of two tightly coupled processes: mitosis, in which the cell's chromosomes are divided between the two daughter cells, and cytokinesis, in which the cell's cytoplasm physically divides.

G1 (presynthetic); S (DNA synthesis); G2 (premitotic); M (mitotic phase) Quiescent cells are in a physiologic state called G0.

 Cell death of non-proliferating (static) cells is

defined 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 reproductive integrity (reproductive death). A surviving cell that maintains its reproductive integrity and proliferates almost indefinitely is said to be Clonogenic.

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.

 A cell survival curve describes the relationship

between the surviving fraction of cells (i.e. the fraction of irradiated cells that maintain their reproductive integrity (clonogenic cells) and the absorbed dose. Cell survival as a function of radiation dose is graphically represented by plotting the surviving fraction on a logarithmic scale on the ordinate (y-axis) against dose on a linear scale on the abscissa(x-axis).

 First In Vitro survival curve was reported in 1956 with

much excitement by Puck & Marcus. There were a few skeptics like Dr Spear who believed that the In Vitro behaviour of cells would not survive the test of time In Vivo as evidenced in an historic public lecture he delivered in 1957. The few optimists like Dr David Gould, a Professor of Radiology at the University of Colorado were however vindicated as time passed by when techniques became available In Vivo, the parameters of dose-response relationships were shown to be quite similar In Vitro.

Surviving Cell Fractions are plotted in a logarithmic scale on the Ordinate(y-axis) and radiation dose on the abscissa(x-axis). Type of Radiation influences the SHAPE 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 curvy Shoulder region and .become straight at higher doses with another slope D0.

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

 Various mathematical/biophysical models have been

proposed to describe the shape of the CSC :

A.Linear Quadratic Model This is currently used to

describe the CSC. It assumes that there are two components 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 the constant that describe the initial slope, is the smaller constant that describe the Quadratic component.

 B. Multi-Target Single Hit Model- This is the earlier

model which is assumed to have a little biological basis. It is described by: D1, the initial slope which is said to be due to single event killing. D0, the final slope which is due to multiple event killing(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.

Dq which is called the Quasi-threshold dose is defined as the dose at which the straight portion of the curve extrapolatedbackwards, cuts the dose axis drawn through a survival fraction of unity. Since there is no dose below which radiation dose does not produce any effect( threshold dose), the Dq is the closest thing.