chapter 7 what is radiation biology? - weber state...

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Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 1

Chapter 7

Molecular & Cellular Radiation Biology


What is Radiation Biology?

A branch of biology concerned with how

ionizing radiation effects living systems.

Biological damage that occurs from

different types of ionizing radiation

Charge, mass, and energy vary among

different types of ionizing radiation

Ionizing Radiation

Removing electrons from an Atom.

This ionized Atom will not bond properly

in molecules.

Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 4

Energy Transfer Determinants

LET – Linear Energy Transfer

RBE – Relative Biological Effectiveness

OER – Oxygen Enhancement Ratio

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Linear Energy Transfer (LET)

A method of expressing radiation quality.

kiloelectron volts (keV) per micron (1 micron [µm]

=10-6 m)

A measure of the rate at which radiation energy is

transferred to soft tissue (track).

An important factor in assessing tissue and organ

damage from exposure to ionizing radiation.


Low-LET/High-LET

Low-LET: x-rays – electron shells. Gamma rays -

short-wavelength, high-energy waves emitted by

the nuclei of radioactive substances

High-LET: particles that possess substantial mass

and charge (alpha particles, ions of heavy nuclei,

low-energy neutrons, and charged particles

released from interactions between neutrons and

atoms).

Dense ionization along the length of the track.


Low LET Low LET

It does not relinquish all of its energy

quickly.

Indirect action from free radicals

Less destructive to biological matter.


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High LET High LET

Particles with mass and charge

Dense ionization along the track. More

ionization per unit of distance traveled.

Lose energy more rapidly

More destructive to biological matter.


LET

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Low LET vs. High LET

Low LET More penetration

Less destruction to

biological matter

Gives up less energy

(less interaction)

Less ionizing

Electromagnetic radiation

Indirect action

High LET Less Penetration

More destruction to

biological matter

Gives up more energy

(more interaction)

More ionizing

Particle radiation

Direct action


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Relative Biologic Effectiveness

(RBE)

As LET increases the ability to produce

biological damage also increases.

Radiations with different LETs will

produce different biological effects.

RBE is used for specific experiments

with specific cells or animal tissues.

It is not used for radiation protection

doses in humans.

Relative Biologic Effectiveness

(RBE)

The relative biological effectiveness for

a given test radiation, is calculated as

the dose of a reference radiation

(usually x-rays) required to produce the

same biological effect as was seen with

a test dose, DT, of another radiation.

http://www.hps.org/publicinformation/ate/q647.html.14

RBE - Example

If it took 200 mGy of x rays but only

20mGy of neutrons to produce the

same biological effect, the RBE would

be 200/20 = 10 using x rays as the

reference radiation.

Which means:

The 20 mGy of neutrons is 10 times as

effective in producing the biological

reaction as the 200 mGy of x-ray.

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RBE

For radiation protection purposes, the

International Commission on

Radiological Protection, ICRP, has

described the effectiveness of radiations

of differing qualities by a series of

Quality Factors (ICRP 1977) and more

recently by a series of Radiation

Weighting Factors (ICRP 1991).

16http://www.hps.org/publicinformation/ate/q647.html.

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Radiation Weighting Factors

17http://www.hps.org/publicinformation/ate/q647.html.


Oxygen Enhancement Ratio

(OER)

OER describes the sensitivity of

oxygenated tissue mathematically by

dividing the dose necessary under

anoxic conditions to produce a given

effect by the dose necessary under

aerobic conditions to produce the same

effect.

OER


OER

High LET (direct action) – presence or

absence of oxygen is of no

consequence

Low LET (predominately indirect action)

– the presence of oxygen makes the

damage caused by free radicals

permanent (the oxygen fixation

hypothesis)


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Molecular Effects

Direct Hit – an x-ray photon hits a

critical molecule and damages or kills it

(DNA)

Indirect Hit – an x-ray photon hits a

water molecule and produces a free

radical that hits a critical molecule and

damages or kills it (DNA)


Direct/Indirect Action


INDIRECT HIT THEORY

Water to Hydrogen peroxide

(And kill indirectly)

95% of cellular damage

Module Medical VIII. - 24

Radiolysis of H2O molecule

Shared electron

Shared electron

H-O-H HOH+ + e- (ionization)

H-O-H- H0+OH- (free radicals)

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Module Medical VIII. - 25

Radiolysis of H2O molecule

Shared electron

Shared electron

H-O-H HOH+ + e- (ionization)

H-O-H+ H+ +OH0 (free radicals)

Free Radicals

Configuration of one or more atoms that

have an unpaired electron but no

electrical charge.

Free radicals are formed by the rupture

of a bond in a stable molecule with the

production of two fragments, each with

an unpaired electron. The resulting free

radicals may participate in further

reactions or may combine to reform the

original compound.Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 26

- 27

Reactions with free radicals

OH0 + OH0 H2O2 (hydrogen peroxide)

O2 + H0 HO20 (hydroperoxl) Radical

This free radical and hydrogen peroxide

are among the primary substances that

produce biological damage directly

after interaction of water and radiation.

Target Theory

Master molecule is responsible for the

survival of the cell.

DNA is the master molecule.

Destruction of the master molecule

results in cell death.

Takes more than one hit.


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Cellular Effects of Irradiation

Instant death (1000 Gy)

Reproductive death (1-10 Gy)

Apoptosis, or programmed cell death

(interphase death)

Mitotic, or genetic, death

Mitotic delay (0.01 Gy)

Interference of function

Chromosome breakage

Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 30

Radiosensitive Cells

Lymphocytes

Erythroblasts

Cancer cells

Spermatogonia

Crypt cells of the small intestine


Radioinsensative Cells

Nerve Cells

Muscle Cells

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Cell Sensitivity

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System sensitivity

If a cell type in a system is sensitive, then

the entire system is sensitive

Oxygen Enhancement Effects

Oxygen increases radio sensitivity.

Why would a patient undergoing

radiation therapy treatments also have

hyperbaric treatments?



Law of Bergonie & Tribondeau

RADIOSENSITIVITY is a function of:

Metabolic state of the cell

Differentiation: most mature or

specialized. (inversely proportional)

Reproductive rate (directly proportional)

Radiosensitivity

Least mature

Least specialized

Highly reproductive

Longest mitotic phase

What cells qualify?


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Lympocytes

Leukocytes refers to white blood cells.

Lymphocytes refers to a subgroup.

Provide protection from antigens.

Lymphocytes produced in bone marrow

are the most radiosenstive blood cell in

the human body.


Nerve Tissue

In adults less radiosensitve than in the

embryo-fetus stage.

Adult single dose of 50Gy may lead to

death within a few hours or days.


Nerve Tissue

Radiosensitve during the embryo-fetus

stage of development

Window of maximal sensitivity 8-15

weeks after gestation.

Lower risk from this stage through 25

weeks.

After 25 weeks risk not found to be

significantly different from that of young

adults. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 39

Reproductive cells

Radiosensitive.

Irradiation can cause depression to sterility in

men.

Dose as low as 0.1Gy in a male could

depress sperm count or cause genetic

mutations in future generations.

Dose of 5Gy in women can cause sterility in

woman.

Women 20-30 exhibit the lowest degree of

sensitivity


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Questions?

41

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