Ahmed GroupLecture 1 MAMMALIAN RADIATION BIOLOGY COURSE Lecture 1 INTERACTION OF RADIATION WITH BIOLOGICAL SYSTEMS

Ahmed GroupLecture 1

MAMMALIAN RADIATION BIOLOGY COURSE

Lecture 1INTERACTION OF RADIATION WITH BIOLOGICAL

SYSTEMS


TOPICS COVERED IN THIS LECTURE

• Definition of ionizing radiation• Types of ionizing radiation and non-ionizing radiation• Definition of LET and quality of ionizing radiation• Generation of free radicals• Direct and indirect action of ionizing radiation


Definition of ionizing radiation


Radiation Biology Radiation Biology A study of the action of ionizing radiation on living thingsA study of the action of ionizing radiation on living things

30-100 Trillion Cells at Risk30-100 Trillion Cells at Risk30-100 Trillion Cells at Risk30-100 Trillion Cells at Risk

• Different Cell TypesDifferent Cell Types• Different Cell CycleDifferent Cell Cycle• Different Cell TargetsDifferent Cell Targets

• Different Cell TypesDifferent Cell Types• Different Cell CycleDifferent Cell Cycle• Different Cell TargetsDifferent Cell Targets

LD/50 = 4 GyLD/50 = 4 Gy4 Gy = 67 calories4 Gy = 67 calories67 calories = 3 ml sip of 60°C coffee67 calories = 3 ml sip of 60°C coffee


RADIATION

Radiation is the term given to the energytransmitted by means of particles or waves.

It can be ionizing or non-ionizing


IONIZING RADIATION

The absorption of energy from radiation in biologic material may lead to excitation or to ionization.

If the radiation has sufficient energy to eject orbital electrons from the atom or molecule, the process is called ionization and that radiation is said to be

Ionizing Radiation


The important characteristic of ionizing radiation is the localized release of large amounts of energy.

The energy per ionizing event – 33 eV – well enough to breaka chemical bond (ex. C=C bond is 4.9 eV).




IONIZING RADIATION

• Electromagnetic

• Particular

X-rays (produced extra-nuclearly)γ-rays (produced intra-nuclearly)

ElectronsProtonsα-ParticlesNeutronsDeuteronsHeavy charged particles

X-rays and γ-rays do not differ in nature or in properties, only in the way they are produced


X-rays are electromagnetic waves

λν=c

All forms of electromagnetic radiation have the same velocity, but different wavelength, and therefore different frequencies

λ - wavelength ν - frequency c - velocity


The Electromagnetic SpectrumLike X-rays, radio waves, radar, radiant heat, laser and visible light are forms of electromagnetic radiation. They have the same velocity but different wavelengths.

For example, radio wave have a wavelength of 300m; visible light - 5x10-5; X-rays - 1x10-8cm.


X-rays may be thought of as electromagnetic waves and-alternatively- as streams of photons, or “packets” of energy

Each energy packet contains an amount of energy equal

to E=hν, where h is Planck’s constant and ν is the frequency

If a radiation has a long wavelength, it has a small frequency (λν=c),and so the energy per photon is small. Conversely, radiation with short wavelength will have a large frequency and hence the energy perphoton is large.

In their biological effects, electromagnetic radiations are consideredto be ionizing if they have a photon energy in excess of 124 eV, which corresponds to a wavelength shorter than about 10-6 cm.


Electromagnetic Spectrum


Electromagnetic Spectrum


Mass = 70kg

LD/50/60 = 4Gy

Energy absorbed = 70 x 4 = 280 joules 280 = 67 calories4.18

Mass = 70 kg

Height lifted to equal the energy in the LD/50/60 = 28070 x 0.0981= 0.4 m (16 inches)

Excess temperature (0C) = 60 - 37 = 23Volume of coffee consumed to equal the energy in the LD/50/60 = 67

23 = 3 ml = 1 sip

The biologic effect of radiation is determined by the photon size of the energy, not by the amount of energy absorbed. Lethal dose of 4Gy corresponds to only 67 cal of the total energy absorbed


Particulate Radiations

ElectronsProtonsα-ParticlesNeutronsDeuteronsHeavy charged particles

These types of radiation occur in nature and also are usedexperimentally, in radiation therapy and diagnostic radiology


Alpha Radiation ()• Nuclei of helium atoms• 2 protons and 2 neutrons• Heavy, slow, +2 charge• Can be accelerated in electrical devices similar to

those used for protons• High linear energy transfer (LET)• Low penetrability• They are also emitted during the decay of heavy

naturally occuring radionuclides:

210

84

206

82

4

2Po Pb + He


Decay of a Heavy Radionuclide by the Emission of an α -particle

The emission of an α-particle (two protons and two neutrons) decreases the atomic number by two and the mass number by four.

Note that the radium has changed to another chemical element, radon, as a consequence of the decay.


Beta Radiation ()

• Electron emitted from nucleus• Light, Fast, -1 charge• Can be accelerated to high energies in betatron or linear

accelerator. Widely used in cancer therapy• Can travel several feet in air and has a medium penetrability• The range of beta particle is considerably greater than an

alpha particle• Beta particle may transfer energy through ionization,

excitation and it can produce a Bremsstrahlung radiation (X-rays)


Alpha particles and beta particles are cosidered directly ionizing because they carry a charge and can, therefore, interact directly with atomic electrons through coulombic forces (i.e. like charges repel each other; opposite charges attract each other).


Neutrons (n)• Neutral particle• Classified by energy:

• Thermal neutrons – E < 1eV• Fast neutrons – E > 10 keV• Indirectly ionizing (no electrical charge). Ionization is caused by charged particles,

which are produced during collisions with atomic nuclei• Neutrons are also emitted as byproducts of fission of heavy unstable radioactive atoms.

With the exception of 209 Bi each nucleus with an atomic number greater than 82 is unstable.

• Neutrons interaction depends on the neutron energy and the material of the absorber: Scattering: elastic and inelastic; capture; spallation


Photon

Neutron

Alpha particle

Various trajectories and target


Interaction of photons with matter

• Photons have zero mass, zero charge, and a velocity that is always “c”, the speed of light;• They do not steadily lose energy via coulombic interactions with atomic electrons as do charged particles;• Photons travel considerable distance before transferring the photon energy to electron energy;• Photons are far more penetrating than charged particles of similar energy.


Absorption of an X-ray photon by the Compton process

The process by which X-ray photons are absorbed depends on the energy of the photons and the chemical composition of the absorber.

At high energies (100 keV-10 MeV) characteristic of a cobalt-60 unit or a linear acceleratorused for radiotherapy, the Compton process dominates

Part of the photon energy is given to the electron as kinetic energy. The photon proceeds with reduced energy


Absorption of an X-ray photon by the photoelectric process

The photon gives up its energy entirely; the electron is ejected from the atom. The vacancy is filled either by an electron from an outer orbit or by a free electron from outside the atom. The change in

energy is emitted as a photon of characteristic X-rays.

It is a predominant mode ofphoton interaction at:• relatively low photon energies• high atomic number Z


Absorption of neutronselastic collision

Neutrons lose their energy by elastic collision with nuclei of similar mass. In soft tissues interaction of a fast neutron with the hydrogen nuclei (protons) is the dominant process of energy transfer. Part of the energy of the neutron is given to the proton as kinetic energy. Deflected neutron proceeds with reduced energy.


Inelastic scattering

At energies above 6MeV inelastic scattering contributes to energy loss in the absorbing material. The neutron may interact with carbon or oxygen nucleus to produce three of four α-particles. These are known as spallation products which are very important at higher energies.


NON-IONIZING RADIATION

Can cause excitation of atoms where electrons jump to higher atomic energy levels but are not removed from the atom:

- UV light- Lasers- Microwave- Radio waves- Infrared Waves


LASER - Light Amplification by Stimulated Emission of Radiation

• Light - describes all types of energy emitted from a laser; visible and invisible• Amplification - of electromagnetic energy necessary to produce a very high intensity laser beam• Stimulated Emission - process that occurs at the atomic level, by which electromagnetic energy is amplified• Radiation - describes how energy is transferred. Does NOT refer to x-rays or gamma rays.

CHARACTERISTICS OF LASER LIGHT

• Monochromatic - when laser light is passed through a prism, no separation occurs• Directional - all laser energy travels in the same direction• Coherent - rays of laser energy travel together without interfering with one another


Interactions of the Laser with Matter

1. Can be absorbed, reflected or transmitted2. Reflection of laser energy from material surfaces occurs in

2 ways - Specular - interacts with smooth surfaces and maintains

most of the original beam of energy - Diffuse - interacts with coarse surfaces and disperses

the energy in many directions3. The further laser energy travels within a given material, the

more likely the energy will be absorbed within the material - The laser wavelength and the material with which it

interacts determine what percentage of laser energy will be absorbed, reflected or transmitted


Ultraviolet Radiation




Linear Energy Transfer (LET)

is the energy transferred per unit length of the track.

Unit for LET is keV/µm-kiloelectron volt per micrometerof unit density material.

L=dE/dl, where dE-energy transferred by a charged particleof specified energy in traversing a distance of dl


Optimal Linear Energy Transfer (LET):

Radiation with LETof 100 keV/µM is the most efficient in producing biological damage.The average separationbetween ionizing eventscoincides with the diameterof the DNA double helix


The deposition of energy of different types of radiation

• A 1-MeV electron, produced for example, by photons of cobalt-60- -rays. The particle is very sparsely ionizing.

• A 5-keV electron, typical of secondary electrons produced by x-rays of diagnostic quality. This particle is also sparsely ionizing but a little denser than the higher-energy electron.

•A 10-MeV proton, typical of the recoil protons produced by high-energy neutrons used for radiotherapy. The track is intermediate in ionization density.

•A 500-keV proton, produced by lower energy neutrons (e.g., from fission spectrum) or by higher-energy neutrons after multiple collisions. The ionizations form a dense column along the track of the particle.

Sparsely ionizing track of a fast electron in a cloud chamberSparsely ionizing track of a fast electron in a cloud chamber

Densely ionizing track of an alpha particular in a cloud chamberDensely ionizing track of an alpha particular in a cloud chamber


low LET (, x, ~)

high LET (, n, ~)

air tissue

inci

dent

rad

iatio

n

greater radiotoxicity

dispersion of energy

LET = linear energy transfer

The deposition of energy of different types of radiation


Typical Linear Energy Transfer Values




Radiation interaction with water

HOH+ + e-HOH

HOH + e- HOH-

HOH+ H+ + OH•*

HOH-OH- + H•

radiation

Ion pair (H+, OH-)

HOHFree Radicals (H•, OH•)

The cell is composed of 80% water. The ultimate result of radiation interaction with water molecule is the formation of an ion pair and free radicals. Free radicals have an unpaired electron in their outer shell, a state which confers a high degree of reactivity.


X-ray photon fast electron (e) ion radical free radical chemical changes biologic effect

Free radicals initiate chemical reactions that lead to the production of damage via indirect action in the cell. The following outline summarizes the general sequence of events that occurs in the cell via indirect action:




When ionizing radiation interacts with a cell, ionizations and excitations are produced either in critical biological macromolecules (e.g. DNA) or in the medium in which the cellular organelles are suspended (e.g. water, HOH).

Based on the site of these interactions, the action of radiation on the cell can be classified as either direct or indirect.


Electromagnetic radiations such as X- and gamma-rays are indirectly ionizing.

In indirect action the critical site is damaged by reactive species produced by ionizations elsewhere in the cell, which in turn damage the target



Direct action dominates for more densely ionizing radiations such as neutrons because the secondary charged particles produced result in a dense column of ionizations

more likely to interact with DNA.


Sequence of Events in Indirect Action

T1/2 in sec Incident X-ray photons

10-15 Fast electrons

10-5 Ion radicals

10-5 Free radicals

Macromolecular changes frombreakage of chemical bonds

Biological effects

days - cell killinggeneration - mutation

years - carcinogenesis

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Ahmed GroupLecture 1 MAMMALIAN RADIATION BIOLOGY COURSE Lecture 1 INTERACTION OF RADIATION WITH BIOLOGICAL SYSTEMS