(2) Radiation Health Physics Unit 2 - Radiation Biology/ Cellular Effects- Part II

Radiation Biology/ Cellular Effects- Part II

According to the law of Bergonie and Tribondeau, which cells are most radiosensitive?

Cells that divide more and are less differentiated are more sensitive to radiation 

What type of cells are more radiosensitive, stem cells or mature cells?

Stem cells

What type of cells are more radioresistant, stem cells or mature cells?

Mature cells 

Are younger tissues more radiosensitive or radioresistant?

Radiosensitive

How does high metabolic activity affect radiosensitivity?

Increases radiosensitivity

How does a high proliferation rate/high growth rate affect radiosensitivity?

Increases radiosensitivity

What are some highly radiosensitive cells?

1. Lymphocytes

2. Erythroblasts,

3. Ocytes

4. Spermatogonia

What is the most radiosensitive cell?

Lymphocytes

What are the most radioresistant cells?

1. Nerve/brain cells

2. Connective tissues (ligaments, cartilage, tendons)

3. Muscle

What cells are listed as most radioresistant?

Nerve/brain cells

Can cells damaged by radiation be identified by unique cellular changes specific to radiation?

No

A biological response that increases at a constant rate as radiation dose increases us what kind of dose-response relationship?

linear

What dose-response relationship assumes that any radiation exposure carries some risk?

linear

What type of  radiation effects follow a linear nonthreshold response?

Stochastic effects (cancer/genetic effects) 

In a linear nonthreshold model as radiation dose increases, what happens to the probability of stochastic effects?

Increases

What type of radiation effects follow a sigmoidal dose-response relationship?

 Deterministic effects (radiation death and skin effects due to high dose) 

Which type of radiation effect has no threshold?

Stochastic

Which type of radiation effect has a threshold?

Deterministic

Which type of effect is associated with cancer and genetic effects?

Stochastic

Which type of effect is associated with skin injury and radiation death?

Deterministic

The target theory suggests that a crucial molecule (DNA) must be _____ for radiation to cause cell ___

 inactivated, death 

What is the critical target molecule?

DNA

When interaction occurs between radiation and target molecule (DNA) what is caused?

Death of cell or biological damage passing to the next generation 

What is an indirect hit?

 Radiation interacts with water, producing free radicals that damage DNA

Which effect has a larger effective target area?

 Indirect effect

Why does the indirect effect have a larger effective target area?

Free radicals can move and attack DNA

Does radiation act randomly?

Yes

What is cell-survival kinetics?

 The relationship between radiation dose and the fraction of cells surviving

What happens to cell survival as radiation dose increases?

Cell survival decreases

What does the shoulder of a cell-survival curve represent?

 Sublethal damage

What is the single-target, single-hit model?

Each cell has one critical target, and inactivation of that target (DNA) kills the cell. (1 hit is lethal) 

How many targets does each cell have in the single-target, single-hit model?

1

How many hits are needed to kill the cell in a singe-target, single-hit model?

1

What happens when the target is inactivated in a singe-target, single-hit model?

Cell death

What type of survival curve does the single-target, single-hit model produce?

Linear

What type of radiation effect does the single-target, single-hit model represent?

High-LET radiation → leads to Double-strand breaks & cell death 

What is the multitarget, single-hit model?

 Each cell contains multiple critical targets, and all targets must be inactivated to kill the cell.

How many targets does each cell contain in a  multitarget, single-hit model?

Multiple (n) distinct but identical targets

What happens when only one target is inactivated in a multitarget, single-hit model?

Sublethal damage

What must happen for the cell to die in a multitarget, single-hit model?

All n targets must be inactivated

What type of radiation effect is associated with the multitarget, single-hit model?

 Low-LET radiation (not enough to cause double-strand break) causes single-strand breaks

Why is low-LET radiation associated with the multitarget, single-hit model?

Because it often causes sublethal damage, and multiple critical targets must be inactivated before the cell dies.

What does LET stand for?

Linear Energy Transfer

What does LET measure?

Average energy deposited per unit length of radiation track

What is the unit for LET?

keV/µm

What happens to biological damage as LET increases?

Increases

Diagnostic x-rays have an LET of?

3keV/µm

What types of radiation have low LET?

X-rays, gamma-rays, and beta particles

What type of radiation has high LET?

α particles, neutrons, and heavy nuclei

α particles have an LET of?

100keV/µm

When LET is ___ ionizations occur frequently so the probability with the target molecule is higher

high

What does RBE stand for?

 Relative Biological Effectiveness

What does RBE measure?

The effectiveness of radiation at producing a specific biological effect

RBE for x-rays, γ-rays, and electrons is?

1

RBE for neutrons is?

10

RBE for α particles is?

20

What is the formula for LET?

 Energy deposited/distance traveled

What is the formula for RBE?

Dose of reference radiation/dose of test radiation for the same effect

What happens to RBE as LET increases?

 Generally increases until the overkill region

What is the region of overkill?

When additional energy deposition no longer increases biological effectiveness proportionally, causing RBE to decrease

Which radiation causes more densely packed ionizations?

High-LET radiation

Which radiation is more likely to cause indirect damage?

 Low-LET radiation

Which radiation is more likely to cause direct damage?

 High-LET radiation

Which radiation is more likely to cause single-strand DNA breaks?

 Low LET

Which radiation is more likely to cause double-strand DNA breaks?

 High LET

Which radiation is associated with more repairable damage?

 Low LET

Which radiation is associated with more severe, difficult-to-repair damage?

 High LET

The rate at which radiation is delivered is called?

Dose rate

The lower the dose rate the __ the survival?

Higher

Extending the time over which a radiation dose is delivered is called?

Protraction

Delivering radiation in separate doses with time between exposures is called?

 Fractionation

What is the difference between protraction and fractionation?

Protraction extends delivery time; fractionation separates the dose into multiple exposures 

Why do fractionation and protraction generally reduce radiation effects?

They allow time for intracellular repair and recovery to become resistant to radiation effects 

What happens to cell survival with fractionation and protraction?

Cell survival generally increases.

What happens to the biological effectiveness of radiation with fractionation and protraction?

 It generally decreases.

The oxygen effect states that tissue is ___ radiosensitive in an oxygenated (aerobic state)

more

Which tissue is more radiosensitive, aerobic or hypoxic tissue?

Aerobic (oxygenated) tissue

What is the OER formula?

Dose under anoxic conditions/dose under aerobic conditions for the same effect

What happens to OER as LET increases?

OER decreases

What is the approximate OER for low-LET radiation?

3

What is the approximate OER for high-LET radiation?

1

At what age are humans most radiosensitive?

 Before birth

How does radiosensitivity change with age?

Decreases until maturity and increases again in old age

What are the two components of recovery?

 Intracellular repair and repopulation

Which tissue is generally more likely to recover between radiation treatments, healthy tissue or tumor cells?

Healthy tissue

Why is fractionation used in radiation therapy?

To allow healthy tissue to recover between treatments

Agents that enhance the effect of radiation are called?

Radiosensitizers

What is an example of a radiosensitizer?

Oxygen

Compounds that reduce radiation damage are called?

Radioprotectors

What chemical group is associated with radioprotectors in your lecture?

 Sulfhydryl group

What are examples of radioprotective compounds?

Cysteine and cystamine

What stage of the cell cycle is most radiosensitive?

Mitosis because the fraction of surviving cells is lowest in this phase

What stage is most radioresistant?

 Late S phase