Radiation Energy Transfer

Radiation Energy Transfer

Refers to fhe process by which ionizing radiation deposits energy into biologic tissues, initiating physical, and ultimately biological changes

Physical stage

The initial interaction between radiation and matter. This stage occurs in about one quadrillionth of a second

Chemical stage

The ionized atoms and free electrons formed the physical stage begin to interact with surrounding molecules

Biological stage

Cells begin to responds to the molecular damage

Direct and Indirect effect

Molecular damages of radiation

Direct effect

Radiation interacts directly with DNA, causing ionization and molecular damage

Target theory

Cell deaths occur on,y if the critical target molecule is inactiva

Hit

Refers to ionization within the sensitive target area

High LET radiation (alpha particles, neutrons)

- ionizations are closely spaced

- high probability of direct DNA damage

- maximum hits already occur

-oxygens add little effect

Low LET radiation (x-rays, gamma rays)

- ionizations are far apart

- lower chance of direct DNA hit

- oxygen increases effectiveness

Cell survival

We measure ..., not cell death

Cell cloning method

Cell are plated in a Petri dish, incubated 10-14 days, colonies form

Fewer

More radiation dose; ... colonies

- The cell may lose its ability to divide (mitotic death)

- cloning efficiency decreases

- development may fail

If DNA is damaged by radiation:

1. single-target, single-hit model

2. multitarget, single-hit model

Survival curve models

single-target, single-hit model

- one critical target (DNA)

- one hit = cell death

- no repair

- straight survival curve

Multitarget, single hit model

- multiple targets

- all must be hit

- repair possible at low dose

- shoulder in survival curve

Small Do

Cells are very radiosensitive

Large Do

Cells are more radioresistant

Large Dq

More repair capacity

Small Dq

Little repair capacity

Sublethal Damage

Damage that:

- does NOT immediately kill the cell

- can be repaired

- becomes lethal if additional damage occurs before repair

Sublethal Damage Recovery

is the process by which

cells repair radiation damage between exposures.

1. Dose rate

2. LET

Factors affecting recovery

More repair

Low does rate; ... repair

Less repair

High dose rate; ... repair

More

Low LET; ... SLD recovery

minimal

High LET; ... SLD recovery

Fractionation

... in radiation therapy allows repair in normal tissue

Mitotic death (reproductive death)

Most common radiation-induced death

Mitotic death (reproductive death)

- double-strand DNA breaks

- chromosomes aberrations

- failed mitosis

Mitotic death (reproductive death)

Cell dies when attempting division, primary mechanism in radiation therapy

Apoptosis

- programmed cell death

- occurs rapidly

- common in lymphocytes

Necrosis

- uncontrolled death

- occurs at very high doses

-rare in diagnostic imaging

Interphase death

- occurs before mitosis

- cell dies during interphase

- seen in highly radiosensitive cells (lymphocytes)

- Mitotic death

- apoptosis

- necrosis

- interphase death

Types of cell death

Indirect effect

Radiation interacts with water, not DNA directly

Radiolysis of water

Occurs when ionizing radiation interacts with water molecules, causing them to break apart into ion pairs and free radicals

Free radical

an atom or molecule that

has an unpaired electron in the valence shell, making

it highly reactive.

Free radicals

are the primary mediator of the indirect

effects on DNA.

1. Ionization of Water

2. Formation of Free Radicals

Radiolysis of water

Hydrogen ion, hydroxyl ion

The water molecule becomes ionized, forming:

Hydrogen free radical, Hydroxyl free radical

The unstable ionized water molecule further breaks down into free radicals, which are highly reactive:

Hydroperoxyl radical (HO2*), hydrogen peroxide (H2O2)

When oxygen is present it reacts with hydrogen radical and hydroxyl radical and forms:

Oxygen Fixation Hypothesis

Oxygen "fixes" or makes radiation damage permanent, so the cell cannot repair it

1. Linear energy transfer (LET)

2. relative biological effectiveness (RBE)

Physical factors affecting radiosensitivity

Linear Energy Transfer (LET)

Energy deposited per unit track length

keV/um

What is the unit of LET?

Energy deposited/Distance traveled

LET formula

Low LET radiation

- sparse ionization

- mostly indirect effect

- more repairable

- alpha particles

- neutrons

High LET radiation examples

High LET radiation

- Dense ionization

- mostly direct effect

- difficult to repair

Relative Biological Effectiveness (RBE)

A measure comparing the biological effectiveness of different types of radiation

RBE increases

As LET increases, ...

- radiation type

- tissue type

- dose rate

- biological endpoint

RBE depends on:

Dose of reference radiation/ Dose of test radiation

RBE formula

1. Oxygen Effect

2. Age

3. Recovery

4. Chemical Agents

5. Hormesis

Biological factors affecting radiosensitivity

Oxygen effect

a tissue is more sensitive to radiation when

irradiated in the oxygenated, or

aerobic, state than when irradiated under anoxic or hypoxic

conditions

Oxygen Effect

Refers to the phenomenon where cells are more sensitive to radiation in the presence of oxygen than in its absence

Permanent

Oxygen increases the amount of ... DNA damage caused by radiation

Radiation dose in hypoxic condition/ radiation dose in oxygenated condition

OER formula

2.5 - 3

For low LET: OER =

1

For high LET: OER =

- embryonic tissues

- bone marrow

- intestinal epithelium

- germ cells

- lymphocytes

Most radiosensitive tissues

- Mature nerve cells (neurons)

- muscle cells

Most radioresistant cells

1. radiosensitizers

2. radioprotectors

Chemical agents:

Radiosensitizers

- increase radiation effect

- they make cells more sensitive to radiation damage

Radioprotectors

- decrease radiation damage

- they make cells more radioresistant

Hormesis

Low doses of radiation may produce a beneficial biological effect, rather than harm

- divide rapidly

- are undifferentiated

- have long mitotic future

Based on law of Bergonie and Tribondeau, cells are more radiosensitive if they:

hypoxic

... tumors are more resistant

Birth

Humans are most sensitive before ...

Recovery

• due to repair mechanism inherent in the biochemistry

of the cell.

• if the radiation dose is not sufficient to kill the cell

before its next division, the cell will recover from the

sublethal radiation damage it has sustained.