1. RTMR 284 Chapter 30 : Fundamental Principles of Radiobiology Winter 2012

2. The Law of Bergonie & Tribondeau
1906 French Scientists researching
that Stem cells are MORE radiosensitive
Younger tissues & organs are
radiosensitive
 Metabolic activity,  radiosensitivity
 proliferation & growth rate,
 radiosensitivity
exceptions to the rule that rapidly dividing cells are more sensitive to ionizing radiation:
1. some rapidly growing tumors are insensitive to radiation
2. lymphocytes which divide only occasionally are among the most radiosensitive. don't know why.

3. Physical Factors Affecting Radiosensitivity
LET - Linear Energy Transfer
RBE - Relative Biologic Effectiveness
Fractionation & Protraction

4. Linear Energy Transfer (LET)
Amount of energy transferred to tissue
per distance traveled in that tissue.
LET effects the biological damage
produced in tissue by ionizing radiation
As the LET increases the biological
response increases
Diagnostic x-rays are in the 3.0 LET range
Fast neutrons are in the 50 LET range
Heavy nuclei are in the 1,000 LET range
LET is the amount of energy transferred to tissue per distance traveled in that tissue. Since the amount of ionization and the tissue effects that result from that ionization , are related to the amount of energy absorbed by the patient, linear energy transfer affects the amount of biological damage produced in us by ionizing radiation.

5. LET Scenarios
Slow-moving, highly charged particles have a high rate of LET
produce more ionization in shorter distance
Fast-moving, lower charged particles travel further and deposit less energy.
They have a low LET & cause less damage

6. Relative Biologic Effectiveness (RBE)
RBE measures the damage done to the tissue
As LET increases, RBE increases
The RBE for diagnostic x-rays is 1
The maximum RBE is ~3
When mice are irradiated with 250 kVp x-rays 650 rad is needed for death
with fast neutrons, only 210 rad is needed.

7. Fractionation & Protraction
Two ways to reduce patient exposure
Fractionation:
high dose, with breaks in-between doses
Protraction:
the dose is delivered continuously but at a lower dose rate until all of the dose is given.

8. Fractionation & Protraction Example
Example - mouse irradiation:
600 rad given in 3 min (200 rad/min)
lethal
600 rad 200 rad/min in 12 fractions of 50 rad each separated by 24 hours
non-lethal
fractionation
600 rad 1 rad/min continuously
protraction

9. Biologic Factors Affecting Radiosensitivity
Oxygen effect
Age
Sex
Recovery
Chemical Agents

10. Oxygen Effect
When tissue is in the oxygenated state (aerobic) tissue is most sensitive
(low LET)
Low oxygen state
(hypoxic)
tissue is less sensitive
No oxygen state
(anoxic)
tissue is the most resistant

11. Comments Tissue is more sensitive with oxygen present and LOW LET
With high LET the oxygen being present makes no difference as high LET is so bad already
Sometimes they combine the HBO (hyperbaric chamber) with radiation therapy to make the tissue more oxygenated

12. Biologic Factors: Age and Sex
Humans are most sensitive to radiation before birth and as infants
Least sensitive to radiation in adulthood
Humans are more radiosensitive again in old age
Women appear to be ~5% LESS radiosensitive than men
born with all their eggs, however
sperm reproduces

13. Recovery
If tissue or organ receives a major radiation dose, it will atrophy.
Some cells die and are removed as waste.
Human cells recover from radiation damage in two ways:
Repair
Repopulation

14. Repair & Repopulation Repair
repair mechanism is inherent in the biochemistry of the cell
cells are capable of repair, if the dose doesn’t kill the cell
Repopulation
surviving cells repopulate
what if surviving cells are damaged?

15. Chemical Agents
Some chemicals modify how cells, tissues, & organs respond to radiation
usually need to be present at irradiation
Radiosensitizers
enhance the effect of radiation
make body more sensitive to radiation
Radioprotectors
decrease the effect of radiation
make the body less sensitive to radiation
No human application (protector is toxic)
-some chemicals can modify how cells, tissues, and organs respond to radiation. for this to happen the chemical agents usually have to be present at the time of irradiation.
-using the chemical agent after the exposure will not usually change the radiation response.
radiosensitizers
agents that enhance the effect of radiation are called sensitizing agents.
---if 90% of a cell culture is killed by 200 rad .. if the chemical agent is present then only 100 rad would be needed for the same result.
-one example of this is vitamin k
radioprotectors
-radioprotective agents have not found human application because, they would have to be given in a toxic dose in order to be effective.
--if 500 rad is needed to produce an effect, then with the chem present, 1000 rad would be needed to produce the same effect.
-the protective agent would be worse than the radiation.

16. Radiation Dose-Response Relationships
A dose-response relationship is a graphic relationship between levels of radiation dose & the result of that dose
Linear
Nonlinear
threshold
nonthreshold

17. Linear dose-response relationships

18. Dose-Response Relationships
Threshold
The line on the graph starts higher than 0
Everything below 0 is considered to have no observable response
There is a threshold where no response is expected
Nonthreshold
Any dose, no matter what its size, is expected to produce a response
1.a. nonthreshold dose-response ...
any dose, no matter what its size, is expected to produce a response.
b. nonlinear, nonthreshold
see p no threshold, varied shape
2.a. threshold....
the line on the graph starts at a higher level, greater than zero. everything below that starting point is considered to have no observable response. so there is a threshold where no reaction will occur
2 b. nonlinear threshold
is a threshold, varied shape.

19. Diagnostic Radiology’s Dose-response Relationship
Linear non-threshold is used
Why?
Cannot directly measure low-dose response, so extrapolate information
Safest assumption to make (no threshold)
Overestimate the risk , use it to establish protection guidelines
Conservative approach

20. THE END
Next week Chapter 31
Molecular Radiobiology
Have a Good Week….