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Who are Puck and Marcus?
Irradiated human cervical (HeLa) cells in a Petri dish and led to the development of cell survival curves
What did Puck and Marcus contribute to radiation biology?
Cell survival curves
What are the three outcomes observed when a cell population is irradiated?
Lethal damage, sublethal damage, or no damage
What happens to cells that are lethally damaged?
All targets are hit and the cell dies
What happens to cells that are sublethally damaged?
A few targets are hit and the cell may repair damage
What happens to cells with no damage?
No targets are hit and the cell survives
What happens as radiation dose increases?
The probability of cellular targets being hit increases
What is the Law of Bergonie and Tribondeau?
Ionizing radiation is more effective against actively mitotic, undifferentiated cells with a long mitotic future
Which cells are most radiosensitive according to Bergonie and Tribondeau?
Actively dividing, undifferentiated cells with long mitotic future
What does enhanced response to radiation indicate?
Radiosensitivity
What does diminished response to radiation indicate?
Radioresistance
What are the three groups of factors influencing radiation response?
Physical, chemical, and biologic factors
What do these factors affect?
Cellular radioresponse and the shape of survival curves
What happens to the shoulder region (Dq) with high LET radiation?
It decreases or may be absent
How do survival curves appear with high LET radiation?
Steeper (lower Do)
Why does LET affect biologic response?
Due to differences in energy deposition density in the cell
What is the second physical factor influencing radioresponse?
Dose rate
When is dose rate effect significant?
With low LET radiation (x-rays and gamma rays)
Is dose rate effect seen with high LET radiation?
No
What are the two types of chemical factors affecting radiation response?
Radiosensitizers and radioprotectors
What do radiosensitizers do?
Enhance radiation response
What do radioprotectors do?
Decrease radiation response
What is the most potent radiosensitizer?
Oxygen
When must oxygen be present to be effective?
During radiation exposure
When is oxygen effect most significant?
With low LET radiation
What happens as oxygen levels decrease?
Cell response decreases and survival curve shifts right
What happens to Dq and Do when oxygen decreases?
They increase
With what radiation types is oxygen effect most pronounced?
X-rays and gamma rays
What is the Oxygen Enhancement Ratio (OER)?
Ratio of radiation dose under hypoxic conditions to dose under oxic conditions for the same effect
What is the typical OER for x-rays and gamma rays?
2.5 to 3.0
How much more resistant are hypoxic cells?
2.5 to 3 times more resistant than oxic cells
what is the most important group of radioprotectors?
Sulfhydryls (free sulfur compounds)
When must radioprotectors be present?
During irradiation
When are radioprotectors usually given?
30 minutes before exposure
With which radiation are sulfhydryls most effective?
Low LET radiation
What are the two main biological factors influencing radiation response?
Cell cycle position and ability to repair sublethal damage
When are cells most radiosensitive in the cell cycle?
G2 and M phases
When do cells have intermediate sensitivity?
G1 phase
When are cells most radioresistant?
S phase (especially late S)
What happens to cell survival when radiation is given in fractions?
Cell survival increases
Why does fractionation spare normal tissue?
Allows repair of sublethal damage in normal cells
How does hypoxia affect repair?
Reduces ability to repair sublethal damage
Why is tumor response favorable with fractionation?
Hypoxic tumor cells repair less effectively
How long does sublethal damage repair take after low LET radiation?
Several hours depending on dose per fraction