Survival Curves and Cell DeathEhsan H. Balagamwala, C. Marc Leyrer, Jeffrey A. Kittel, and Alex Almasan


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CELL SURVIVAL CURVES AND CELL DEATH


EHSAN H. BALAGAMWALA, C. MARC LEYRER, JEFFREY A. KITTEL, AND ALEX ALMASAN






 





 





Question 1


What is the most common mechanism of cell death induced by ionizing radiation?







Question 2


How is plating efficiency (PE) defined?







Question 3


What is the importance of calculating the surviving fraction?







Question 4


How does the shape of the cell survival curve differ based on whether sparsely ionizing radiation or densely ionizing radiation is utilized?







 





Question 1 What is the most common mechanism of cell death induced by ionizing radiation?


Answer 1


Mitotic cell death is the most common mechanism for triggering cell death after exposure to ionizing radiation. The biochemical steps may overlap with those encountered during apoptosis (caspase activation, DNA laddering).


Chen Q, Chai Y, Mazumder S, et al. The late increase in free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction. Cell Death Differ. 2003;10:323–334.


Vakifahmetoglu H, Olsson M, Zhivotovsky B. Death through a tragedy: mitotic catastrophe. Cell Death Differ. 2008;15:1153–1162.







Question 2 How is plating efficiency (PE) defined?


Answer 2


PE indicates the percentage of plated cells in a cell culture that grow into colonies. It is defined as:



Hall EJ, Giaccia AJ. Cell survival curves (chap 3). In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:135–153.







Question 3 What is the importance of calculating the surviving fraction?


Answer 3


The surviving fraction is important in generating cell survival curves. Cell survival curves plot the surviving fraction against dose. In the laboratory, experiments can be done to determine the impact of varying radiation dose on cell survival. The surviving fraction can be calculated using:



Hall EJ, Giaccia AJ. Cell survival curves (chap 3). In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:135–153.







Question 4 How does the shape of the cell survival curve differ based on whether sparsely ionizing radiation or densely ionizing radiation is utilized?


Answer 4


With sparsely ionizing (low linear energy transfer) radiation such as x-rays, the cell survival curve on a log-linear plot starts off as a straight line, indicating surviving fraction is an exponential function of dose. As radiation dose increases, the curve bends over a range of doses (until straightening out again at very high doses per fraction), indicating the radiation has become more effective at cell kill per unit dose increase at higher doses.


With densely ionizing (high linear energy transfer) radiation such as α-particles, the cell survival curve is linear from the origin, indicating that cell kill remains an exponential function of dose.


Hall EJ, Giaccia AJ. Cell survival curves (chap 3). In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:135–153.







 





Question 5


What are the two most important biophysical models that explain the shape of cell survival curves?







Question 6


In the multitarget model of cell survival, what do the quantities D0, D1, Dq, and n represent?







Question 7


As the intrinsic radiosensitivity of cells increases, how does D0 change?







 





Question 5 What are the two most important biophysical models that explain the shape of cell survival curves?


Answer 5


The two most important models are the multitarget model and the linear-quadratic model.


Hall EJ, Giaccia AJ. Cell survival curves. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:135–153.







Question 6 In the multitarget model of cell survival, what do the quantities D0, D1, Dq and n represent?


Answer 6


Both the multitarget model and the linear-quadratic model aim to explain the shape of the cell survival curve, which can be determined using in vitro experiments. In the multitarget model, D1 is the initial slope of the curve and represents cell kill from single-hit events. D0 is the final slope of the cell survival curve and represents cell kill from multiple-hit events. Both D0 and D1 represent the dose required to reduce the fraction of surviving cells to 0.37. Since the surviving fraction is on a logarithmic scale, the dose required to reduce the cell population by a given factor (0.37) is the same at all survival levels. The extrapolation number, n, is a measure of the width of the shoulder of the cell survival curve. Dq represents the quasi-threshold dose, which is the dose at which the discrete portion of the survival curve when extrapolated backwards cuts the dose axis at 100% survival. These three parameters are related by:



Hall EJ, Giaccia AJ. Cell survival curves. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:135–153.







Question 7 As the intrinsic radiosensitivity of cells increases, how does D0 change?


Answer 7


Radiosensitive cells have a lower D0 compared to radioresistant cells, which have a higher D0.


Hall EJ, Giaccia AJ. Cell survival curves. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologist. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:135–153.





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Mar 28, 2017 | Posted by in GENERAL RADIOLOGY | Comments Off on Survival Curves and Cell DeathEhsan H. Balagamwala, C. Marc Leyrer, Jeffrey A. Kittel, and Alex Almasan
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