DOSE-RESPONSE RELATIONSHIP

Dose-respose relationship

A mathematical & graphic function that relates radiation dose to observed response

Used to provide the basis for radiation dose management activities

Important applications

Used to design therapeutic treatment routines for patient with cancer

Provides the basis for radiation control activities

Threshold or nonthreshold, linear or non-linear

two characteristics

Linear

The response is directly proportionate to the dose

Radtech field = no safe exposure

Lower Dose: lower response
Higher Dose: Higher response

Response

Y AXIS

Dose

X AXIS

Below zero

papunta sa zero (x axis)

Carcinogenic

Radiation is?

Natural response

no dose but with response

Nonlinear

The response is not directly proportional to the dose

Variable responses from variable doses

sigmoid. s-shaped

Radiation-induced death

High dose = high response (but…)

High dose = overkill

Peak of curve

Threshold

The level below which there is no response

Threshold dose

Dt

At Dt

Intersects the dose axis greater than zero

Below Dt

no response is observed

Erythema

2.0 Gyt (partial irradiation)

Radiation-induced death

2.0 Gyt (Whole Body)

Non-threshold

Any dose, regardless of its size, is expected to produce a response

Intersects the dose axis at zero or below

Indicates that no level of radiation can be considered completely safe

Non-threshold

You don’t know the threshold

Hospital

Linear Non-Threshold

Fluoro, Interventional RadThera, CT-fluoro

deterministic modality

Linear threshold

impossible

overkill

no pathology

Linear Non-Threshold

Basis for radiation protection guidelines

Basis for current dose limits

The results of extrapolation

Radiation-induced cancer

Single-hit chromosome aberration

Linear Nontreshold

Stochastic effects of radiation

• Radiation-induced leukemia

• Radiation induced genetic effect/damage

• Radiation-induced malignant disease

• Radiation-induced thyroid cancer

• Radiation-induced life-span shortening

• Chronic lymphocytic leukemia

50 mSv/ year

radtech dose limit

Nonlinear-nonthreshold

Multihit chromosome aberration

Non-linear threshold

Deterministic effects of radiation

• Radiation-induced cataracts

• Acute radiation syndrome

• Radiation-induced death

• Skin effects fromhigh-dose fluoroscopy

Late deterministic effect

Radiation-induced cataracts

1000 rads

cataract

Less than 10 rads

hormesis

Latent period

15 years

di nagpaparamdam

No response, cellular transformation, cell death

EFFECTS OF RADIATION ON CELLS

No response

Most effect on cells

Because of recovery and repair metabolic processes

Cellular transformation

May result in stochastic effect at the human level

Cell death

May result in deterministic effect at the human level

Effects of Radiation on Cells

Chromosome breakage

Reproductive death (1-10 Gyt)

Apoptosis (few cGyt)

Mitotic or genetic death

Mitotic delay (0.01 Gyt)

Interference with function

Instant death (1000 Gyt)

1-10 Gyt

Reproductive death

few cGyt

Apoptosis

0.01 Gyt

Mitotic Delay

1,000 Gyt

Instant death

Main-chain scission, cross-linking, point lesion

IRRADIATION OF MACROMOLECULES

Main-chain scission

Breakage of the backbone of the long-chain macromolecules

Size: decrease

Viscosity: decrease

Cross-linking

Side spurs attachment to another neighboring macromolecules

bigger macromolecule

bony spur

Viscosity: increase

Point Lesions

Molecular lesions of DNA

Change or loss of a base

Not detectable

Can be produced by free radicals

Point lesions results

• Minor modification of the molecule

• Malfunction within the cell

• Abnormal gene

Laboratory examination

checking viscosity (stickiness)

Damage to DNA

Visible chromosome aberrations (DNA severely damage)

• Dicentric formation

• Terminal deletion

• Ring formation

Dicentric formation, Terminal deletion, Ring formation

DAMAGE TO DNA

Radiation Response of DNA

1. Main-chain scission with only one side rail severed

2. Main-chain scission with both side rails severed

3. Main-chain scission and subsequent cross-linking

4. Rung breakage causing a separation of bases

5. Change in or loss of a base

Target Theory

For a cell to die after radiation exposure, its target molecule must be inactivated

Used to represent cell lethality

Target

an area on the cell occupied by the target molecule or by a sensitive site on the target molecule

Hit

An ionization that inactivates the target

Occurs when radiation interacts with the target molecule (inactivate)

Occurs through both direct & indirect effect

Low LET, Direct Effect, No Oxygen

LOW probability of hit

Relatively large distances between ionizing event

Low LET, Indirect Effect, With Oxygen

HIGH probability of hit

Formation of free radical

Enlarged volume of effectiveness surrounding each ionization

High LET, Direct Effect, No Oxygen

HIGH probability of hit

Close distance between ionization event

High LET, Indirect Effect, With Oxygen

NO additional hits

The maximum number of hits has already been produced by direct effect with high- LET radiation