Radiation Therapy

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RadiobiologyRadiobiology

A PreviewA Preview

By: Katherine Walz

Callie Widmayer

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Ionizing RadiationIonizing Radiation

Ionizing Radiation Ionizing Radiation is the removal of is the removal of an electron from an electron from an atom leaving an an atom leaving an unstable molecule unstable molecule which may then which may then break apart to form break apart to form free radicals.free radicals.

http://www.paradigmlink.com/ionrad.shtml

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Linear Energy Transfer (LET)Linear Energy Transfer (LET)

The average energy deposited per The average energy deposited per unit length of track.unit length of track.

Measured in kiloelectron volts per Measured in kiloelectron volts per micron (10micron (10-6-6 m) m)

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Low LET / High LETLow LET / High LET

Low LETLow LET– Low mass, increased Low mass, increased

travel distance (gamma travel distance (gamma rays, x-rays).rays, x-rays).

– Sparsely ionizing with Sparsely ionizing with random interactions. random interactions.

– Causes damage Causes damage primarily through primarily through indirect action or may indirect action or may cause single strand cause single strand breaks (which are breaks (which are repairable). repairable).

http://staff.jccc.net/PDECELL/biochemistry/dna.gif

e-

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Low LET / High LETLow LET / High LET

High LETHigh LET– Large mass, decreased Large mass, decreased

travel distance (alpha travel distance (alpha particles, protons, low particles, protons, low energy neutrons).energy neutrons).

– Causes dense Causes dense ionization along its ionization along its path with a high path with a high probability of probability of interacting directly interacting directly with DNA.with DNA.

http://staff.jccc.net/PDECELL/biochemistry/dna.gif

α++

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Alpha particlesAlpha particles The alpha particle has a large mass and consists of two The alpha particle has a large mass and consists of two

protons, two neutrons and no electrons (+2)protons, two neutrons and no electrons (+2) The alpha particle deposits a large amount of energy in a The alpha particle deposits a large amount of energy in a

short distance of travel (about 1-2 inches)short distance of travel (about 1-2 inches) Most alpha particles are stopped by a few centimeters of air, a Most alpha particles are stopped by a few centimeters of air, a

sheet of paper, or the dead layer (outer layer) of skin.sheet of paper, or the dead layer (outer layer) of skin.

Beta particlesBeta particles The beta particle has a small mass and is negatively charged The beta particle has a small mass and is negatively charged

(-1) (-1) Beta radiation causes ionization by displacing electrons from Beta radiation causes ionization by displacing electrons from

their orbits.their orbits. Because of its negative charge, the beta particle has a limited Because of its negative charge, the beta particle has a limited

penetrating ability. Range in air is about 10 feet.penetrating ability. Range in air is about 10 feet.

The following are the most common types of ionizing radiation:The following are the most common types of ionizing radiation:


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Gamma rays/x raysGamma rays/x rays Gamma/ x ray radiation is an electromagnetic wave or Gamma/ x ray radiation is an electromagnetic wave or

photon and has no electrical chargephoton and has no electrical charge Gamma/ x ray radiation can ionize as a result of direct Gamma/ x ray radiation can ionize as a result of direct

interactions with orbital electrons and is transmitted interactions with orbital electrons and is transmitted directly to its target. Because Gamma/ x ray radiation directly to its target. Because Gamma/ x ray radiation have no charge and no mass, it has a very high have no charge and no mass, it has a very high penetrating power. penetrating power.

Neutron particlesNeutron particles Neutron radiation consists of neutrons that are ejected Neutron radiation consists of neutrons that are ejected

from the nucleus and have no electrical chargefrom the nucleus and have no electrical charge Due to their neutral charge, neutrons interact with matter Due to their neutral charge, neutrons interact with matter

either directly or indirectlyeither directly or indirectly Because of the lack of a charge, neutrons have a Because of the lack of a charge, neutrons have a

relatively high penetrating ability and are difficult to relatively high penetrating ability and are difficult to stop. stop.


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The reactions caused by ionizing The reactions caused by ionizing radiation occur rapidly, they are radiation occur rapidly, they are nonselective and random.nonselective and random.

The majority of damage caused by The majority of damage caused by radiation is due to chemical reactions radiation is due to chemical reactions with water within the cell.with water within the cell.

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H2O HOH+

e-

water

electron

Positively charged water

molecule

Radiation reacts with water to produce an electron and a positively charged water molecule.

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H2O HOH+

e- + H2O HOH-

water

negatively charged water

molecule

electron water


molecule

The electron reacts with another water molecule to produce a negatively charged water molecule

1111

H2O HOH+

H+

OH*

e- + H2O HOH-

water


molecule

Hydrogen ion

Hydroxyl radical

electronwater


molecule

The positively charged water molecule dissociates into a hydrogen ion and a hydroxyl radical.

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H2O HOH+

H+

OH*

H* OH-

e- + H2O HOH-

water


molecule

Hydrogen ion

Hydroxyl radical

electron water


molecule

hydrogen radical

Hydroxyl ion

The negatively charged water molecule dissociates into a hydrogen radical and a hydroxyl ion.

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ReactionsReactions

The previous reactions produce free The previous reactions produce free electrons (eelectrons (e--), the ions H), the ions H-- and OH and OH--, , the free radicals H* and OH*.the free radicals H* and OH*.

The fate of these products are…….The fate of these products are…….

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H2O HOH+

H+

OH*

H* OH-

e- + H2O HOH-

HOH+ + e- H2O

The positively charged water molecule and the electron recombine to form water.

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H2O HOH+

H+

OH*

H* OH-

e- + H2O HOH-

H+ + OH- H2O

The ions combine to form water.

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H2O HOH+

H+

OH*

H* OH-

e- + H2O HOH-

H* + OH* H2O

The radicals combine to form water.

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H2O HOH+

H+

OH*

H* OH-

e- + H2O HOH-

OH*

OH* + OH* H2O2

The hydroxyl radical reacts with another hydroxyl radical to form hydrogen peroxide.

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Free RadicalsFree Radicals

A free radical is an atom A free radical is an atom or molecule that has an or molecule that has an unpaired electron in its unpaired electron in its valence shell.valence shell.

These free radicals are These free radicals are non-selective when non-selective when pairing up with electrons pairing up with electrons from other atoms, from other atoms, including those that including those that make up the DNA make up the DNA molecule.molecule.

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Direct Action / Indirect Direct Action / Indirect ActionActionDirect ActionDirect Action

Causes damage directly to DNA or other Causes damage directly to DNA or other important molecules in the cell.important molecules in the cell.

More likely when the beam of charged particles More likely when the beam of charged particles consist of alpha particles, protons, or electrons consist of alpha particles, protons, or electrons

Indirect ActionIndirect Action Causes damage by interacting with the cellular Causes damage by interacting with the cellular

medium producing free radicals which then medium producing free radicals which then damage the DNA molecule.damage the DNA molecule.

More likely when x-rays or gamma-rays More likely when x-rays or gamma-rays compose the beam.compose the beam.

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DNA DamageDNA Damage

The arrangement of nitrogenous bases The arrangement of nitrogenous bases provide a blueprint for DNA for the provide a blueprint for DNA for the synthesis of specific proteins synthesis of specific proteins necessary for individual cell function.necessary for individual cell function.

In the event of a loss or change of one In the event of a loss or change of one or more of the nitrogenous bases, base or more of the nitrogenous bases, base sequence and normal functioning of sequence and normal functioning of the cell is altered.the cell is altered.

Another form of DNA damage due to Another form of DNA damage due to radiation involves a break in the radiation involves a break in the hydrogen bonds between the Adenine hydrogen bonds between the Adenine – Thymine and Cytosine – Guanine – Thymine and Cytosine – Guanine base pairs. These bonds function to base pairs. These bonds function to keep the DNA strands togetherkeep the DNA strands together

Bonds can also break between Bonds can also break between deoxyribose sugar and the phosphate deoxyribose sugar and the phosphate groups which can lead to cross-linking groups which can lead to cross-linking of DNAof DNA

2121http://www.greenfacts.org/glossary/def/dna.htm

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Chromosome AberrationsChromosome Aberrations If the chromosome fragments are If the chromosome fragments are

near one another they have a high near one another they have a high chance of reattaching in their chance of reattaching in their original position – causing no original position – causing no future damage to the cell. A future damage to the cell. A process known as restitution.process known as restitution.

In translocations and inversions, In translocations and inversions, no genetic information is lost, but no genetic information is lost, but the rearrangement of gene the rearrangement of gene sequence will alter protein sequence will alter protein synthesis.synthesis.

In a deletion, a chromosome In a deletion, a chromosome fragment is not replicated during fragment is not replicated during the next mitosis, the genetic the next mitosis, the genetic information is lost. The effects information is lost. The effects this has on the cell depends on this has on the cell depends on the amount and type of the amount and type of information lost.information lost.

Translocation

Inversion

Deletion

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RadiosensitivityRadiosensitivity

Actively reproducing cells are more Actively reproducing cells are more radiosensitive than mature cells.radiosensitive than mature cells.

During mitosis, the cell is in a During mitosis, the cell is in a stressed state and shows an increase stressed state and shows an increase in damage caused by radiation.in damage caused by radiation.

Cells that have decreased levels of Cells that have decreased levels of differentiation are more differentiation are more radiosensitive than specialized cells.radiosensitive than specialized cells.

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FractionationFractionation

Instead of a single Instead of a single treatment consisting of a treatment consisting of a high dose, fractionation high dose, fractionation divides the dose to be divides the dose to be delivered over a period of delivered over a period of time, usually 6-8 weeks.time, usually 6-8 weeks.

At low doses of radiation, At low doses of radiation, normal cells have an normal cells have an increased survival rate increased survival rate because of their ability to because of their ability to repair sublethal damage repair sublethal damage before the next fraction of before the next fraction of radiation is delivered.radiation is delivered.

Tumor cells do not possess Tumor cells do not possess the repair enzymes the repair enzymes necessary to keep up with necessary to keep up with the repairs and as a result the repairs and as a result the cell is overwhelmed.the cell is overwhelmed. http://www.usoncology.com/CompanyInfo/PhotoLibrary.asp

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ReferencesReferences

Leaver, D., Washington C.M. (2004) Principals and Practice of Leaver, D., Washington C.M. (2004) Principals and Practice of Radiation Therapy. Second Edition pp. 55-84 St Louis, MosbyRadiation Therapy. Second Edition pp. 55-84 St Louis, Mosby

Statkiewicz Sherer, M.A., Ritenour, E.R., Visconti, P.J. (2002) Statkiewicz Sherer, M.A., Ritenour, E.R., Visconti, P.J. (2002) Radiation Protection in Medical Radiography. Fourth Edition, Radiation Protection in Medical Radiography. Fourth Edition, pp85-154, St. Louis, Mosby.pp85-154, St. Louis, Mosby.

Ott, M.E. (2006, April 12) Radiation and why it is bad for Ott, M.E. (2006, April 12) Radiation and why it is bad for humans. A videotaped lecture describing Radiation Types, humans. A videotaped lecture describing Radiation Types, Effects & Sources http://video.google.com/videoplay?docid=-Effects & Sources http://video.google.com/videoplay?docid=-1764500297917980309&q=radiation1764500297917980309&q=radiation

Gwozdz, J. T. (2002, July 20). IMRT - Intensity Modulated Gwozdz, J. T. (2002, July 20). IMRT - Intensity Modulated Radiation Therapy. A powerpoint presentation of IMRT Intensity Radiation Therapy. A powerpoint presentation of IMRT Intensity Modulated Radiation Therapy. Modulated Radiation Therapy. http://drjohng.com/Talk/IMRT/Slide1_GIF.htmlhttp://drjohng.com/Talk/IMRT/Slide1_GIF.html

Low Dose Radiobiology Slideshows (n.d.) Low Dose Radiobiology Slideshows (n.d.) http://lowdose.tricity.wsu.edu/radiobio_slideshows.htmhttp://lowdose.tricity.wsu.edu/radiobio_slideshows.htm

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ReferencesReferences

Radiation Therapy. (2003, February). Merck Research Radiation Therapy. (2003, February). Merck Research Laboratories Laboratories http://www.merck.com/mmhe/au/print/sec15/ch182/ch182c.hthttp://www.merck.com/mmhe/au/print/sec15/ch182/ch182c.html) ml)

How Radiation Therapy Works. (n.d.) Physics Students Web How Radiation Therapy Works. (n.d.) Physics Students Web Project of How Radiation Therapy Works Project of How Radiation Therapy Works http://www.unc.edu/~taleb84/phys25/therapy.htmlhttp://www.unc.edu/~taleb84/phys25/therapy.html

Großmann, V. (2004). Radiation Biology and Nanodosimetry Großmann, V. (2004). Radiation Biology and Nanodosimetry http://www.ptb.de/en/publikationen/jahresberichte/jb2004/nachttp://www.ptb.de/en/publikationen/jahresberichte/jb2004/nachrdjahres/s22e.htmlhrdjahres/s22e.html

Medical Physics. (2004). from Johns Hopkins University. Medical Physics. (2004). from Johns Hopkins University. http://www.radonc.jhmi.edu/html/medical_physics.htmlhttp://www.radonc.jhmi.edu/html/medical_physics.html

Radiation Therapy (n.d.) from Wikipedia. Radiation Therapy (n.d.) from Wikipedia. http://en.wikipedia.org/wiki/Radiation_therapy#How_it_workshttp://en.wikipedia.org/wiki/Radiation_therapy#How_it_works

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oh h

o hoh water

water molecule electron

water molecule radiation

ions h

o hoh oh

free radicals h

e water electron