- Cell survival curves relate the radiation dose to the proportion of cells that survive. They are generated through in vitro experiments where cells are exposed to radiation doses and then assessed for their ability to proliferate into colonies. - The linear-quadratic model describes cell survival as having both a linear component related to single radiation hits and a quadratic component related to multiple radiation hits. It is used to design fractionated radiotherapy regimens and understand acute vs late tissue responses. - Key factors in the model include the alpha coefficient representing intrinsic radiosensitivity, the beta coefficient representing repair capacity, and the alpha/beta ratio which indicates the dose where linear and quadratic death are equal.

1. Radiobiology- Cell Survival
Curves
Presenter : Dr. Gowtham Manimaran
Moderator : Dr. Deepak Mittal

2. Contents
• What is a cell survival curve?
• In Vitro Cell survival curve
• Linear quadratic model
• Mechanisms of cell killing

3. Cell Survival curve
• It is a relationship between the radiation dose and the proportion of cells
that survive.
• To understand this ,it is mandatory to define
Cell death
1. For differentiated cells – loss of specific function
2. Proliferating cells – loss of capacity for sustained proliferation
Clonogenic cell – A survivor that has retained its reproductive integrity and
is able to proliferate to produce a colony.

4. In Vitro Cell Survival Curve
• With modern techniques , single cell suspension by the use of enzyme
trypsin is made and grown into what is called as established cell lines.
• Plating efficiency indicates the percentage of cells seeded that grow
into colonies.
• Surviving fraction: Colonies counted / [Cells seeded × (PE / 100)]
A: In this unirradiated control dish, There are 70 colonies; therefore,
the plating efficiency is 70%.
B: Two thousand cells were seeded and then exposed to 8 Gy of x-
rays. There are 32 colonies on the dish. : surviving fraction 32 /
(2,000 × 0.7)= 0.023

5. • The cell culture technique is used to
generate a cell survival curve.
• But it is not adequate to think there
there is only a linear relation between
dose a radiation and the cell changes.
Radiation is believed to affect the
organism as a whole.
• Recently, interest has been renewed in
other effects of radiation like radiation-
induced vascular changes, bystander
effects, and immune cell infiltration
into normal tissues and tumors.

6. Random nature of cell killing
• It is given by Poisson statistics -
indicate that if 100 lethal lesions are
distributed randomly throughout
100 equally radio-sensitive cells, 37
cells will be spared
• A dose of radiation that induces an
average of one lethal event per cell
leaves 37% of irradiated cells still
viable; this is called the D0

7. • For mammalian cells, the x-ray D0 usually lies between 1 and 2 Gy.
• The number and type of DNA lesions per cell detected immediately
after a dose of 1 Gy of x-rays is approximately:
Double-strand breaks (DSBs) 40 – Responsible for cell killing,
carcinogenesis, mutation.
Single-strand breaks (SSBs) 1,000
Base damage >2,000
DNA-DNA crosslinks 30

8. Mammalian Cell
Survival Curve

9. Linear Quadratic Model
• The linear – quadratic model (LQ) was developed by Douglas and Fowler in 1972 [2], it was assumed that cell
death due to ionizing radiation has two components: linear component (αD), directly proportional to dose,
D, characterized by linear coefficient, α, corresponding to the cells that cannot repair themselves after one
radiation hit and it is important for high-LET radiation and quadratic component (βD2 ) directly proportional
to the square of dose characterized by the quadratic coefficient, corresponding to cells that stop dividing
after more than one radiation hit, but can repair the damage caused by the radiation and it is important for
low-LET radiation. The linear coefficient, α indicates the intrinsic cell radiosensitivity, and it is the natural
logarithm (log e) of the proportion of cells that die or will die due to their incapacity to repair radiation-
induced damage of ionizing radiation. The quadratic coefficient, β shows cell repair mechanisms, and it is the
natural logarithm of the proportion of repairable cells due to their ability to repair the radiation-induced
effect of ionizing radiation. In order to formulate equivalent fractionation schemes, to get information on
acute and late responses and also to calculate additional doses after breaks from radiotherapy the LQ model
is used. The early – and late-responding tissues distinction is very important as a result of the recognition
that time–dose relationships are systematically different between them. The α/β ratio is dose for which the
number of acutely responding cell deaths is equal to the number of late-responding cell deaths (the dose for
which the linear and quadratic components of cell death are equal). For tumors and acute effects 3 Clinical
application of linear-quadratic model 787 response in normal tissues, the mean α/β ratio is 10Gy [range 7–
20 Gy]. For late effects in normal tissues, α/β ratio range from 0.5 to 6 Gy [3]; the α/β ratio is not constant,
may differ among tumor types and its value should be carefully chosen [3].