Radiation Therapy

Radiobiology A Preview By: Katherine Walz Callie Widmayer

Ionizing Radiation Ionizing Radiation is the removal of an electron from an atom leaving an unstable molecule which may then break apart to form free radicals. http://www.paradigmlink.com/ionrad.shtml

Linear Energy Transfer (LET) The average energy deposited per unit length of track. Measured in kiloelectron volts per micron (10 -6 m)

Low LET / High LET Low LET Low mass, increased travel distance (gamma rays, x-rays). Sparsely ionizing with random interactions. Causes damage primarily through indirect action or may cause single strand breaks (which are repairable). http://staff.jccc.net/PDECELL/biochemistry/dna.gif e -

Low LET / High LET High LET Large mass, decreased travel distance (alpha particles, protons, low energy neutrons). Causes dense ionization along its path with a high probability of interacting directly with DNA. http://staff.jccc.net/PDECELL/biochemistry/dna.gif α ++

Ionizing Radiation Alpha particles The alpha particle has a large mass and consists of two protons, two neutrons and no electrons (+2) The alpha particle deposits a large amount of energy in a short distance of travel (about 1-2 inches) Most alpha particles are stopped by a few centimeters of air, a sheet of paper, or the dead layer (outer layer) of skin. Beta particles The beta particle has a small mass and is negatively charged (-1) Beta radiation causes ionization by displacing electrons from their orbits. Because of its negative charge, the beta particle has a limited penetrating ability. Range in air is about 10 feet. The following are the most common types of ionizing radiation: http://www.paradigmlink.com/ionrad.shtml

Ionizing Radiation Gamma rays/x rays Gamma/ x ray radiation is an electromagnetic wave or photon and has no electrical charge Gamma/ x ray radiation can ionize as a result of direct interactions with orbital electrons and is transmitted directly to its target. Because Gamma/ x ray radiation have no charge and no mass, it has a very high penetrating power. Neutron particles Neutron radiation consists of neutrons that are ejected from the nucleus and have no electrical charge Due to their neutral charge, neutrons interact with matter either directly or indirectly Because of the lack of a charge, neutrons have a relatively high penetrating ability and are difficult to stop. http://www.paradigmlink.com/ionrad.shtml

Ionizing Radiation The reactions caused by ionizing radiation occur rapidly, they are nonselective and random. The majority of damage caused by radiation is due to chemical reactions with water within the cell.

H 2 O HOH + e - water electron Positively charged water molecule Radiation reacts with water to produce an electron and a positively charged water molecule.

H 2 O HOH + e - + H 2 O HOH - water negatively charged water molecule electron water Positively charged water molecule The electron reacts with another water molecule to produce a negatively charged water molecule

H 2 O HOH + H + OH * e - + H 2 O HOH - water negatively charged water molecule Hydrogen ion Hydroxyl radical electron water Positively charged water molecule The positively charged water molecule dissociates into a hydrogen ion and a hydroxyl radical.

H 2 O HOH + H + OH * H * OH - e - + H 2 O HOH - water negatively charged water molecule Hydrogen ion Hydroxyl radical electron water Positively charged water molecule hydrogen radical Hydroxyl ion The negatively charged water molecule dissociates into a hydrogen radical and a hydroxyl ion.

Reactions The previous reactions produce free electrons (e - ), the ions H - and OH - , the free radicals H* and OH*. The fate of these products are…….

HOH + + e - H 2 O The positively charged water molecule and the electron recombine to form water. H 2 O HOH + H + OH * H * OH - e - + H 2 O HOH -

H + + OH - H 2 O The ions combine to form water. H 2 O HOH + H + OH * H * OH - e - + H 2 O HOH -

H * + OH * H 2 O The radicals combine to form water. H 2 O HOH + H + OH * H * OH - e - + H 2 O HOH -

H 2 O HOH + H + OH * H * OH - e - + H 2 O HOH - OH* OH* + OH* H 2 O 2 The hydroxyl radical reacts with another hydroxyl radical to form hydrogen peroxide.

Free Radicals A free radical is an atom or molecule that has an unpaired electron in its valence shell. These free radicals are non-selective when pairing up with electrons from other atoms, including those that make up the DNA molecule.

Direct Action / Indirect Action Direct Action Causes damage directly to DNA or other important molecules in the cell. More likely when the beam of charged particles consist of alpha particles, protons, or electrons Indirect Action Causes damage by interacting with the cellular medium producing free radicals which then damage the DNA molecule. More likely when x-rays or gamma-rays compose the beam.

DNA Damage The arrangement of nitrogenous bases provide a blueprint for DNA for the synthesis of specific proteins necessary for individual cell function. In the event of a loss or change of one or more of the nitrogenous bases, base sequence and normal functioning of the cell is altered. Another form of DNA damage due to radiation involves a break in the hydrogen bonds between the Adenine – Thymine and Cytosine – Guanine base pairs. These bonds function to keep the DNA strands together Bonds can also break between deoxyribose sugar and the phosphate groups which can lead to cross-linking of DNA

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

Chromosome Aberrations If the chromosome fragments are near one another they have a high chance of reattaching in their original position – causing no future damage to the cell. A process known as restitution. In translocations and inversions, no genetic information is lost, but the rearrangement of gene sequence will alter protein synthesis. In a deletion, a chromosome fragment is not replicated during the next mitosis, the genetic information is lost. The effects this has on the cell depends on the amount and type of information lost. Translocation Inversion Deletion

Radiosensitivity Actively reproducing cells are more radiosensitive than mature cells. During mitosis, the cell is in a stressed state and shows an increase in damage caused by radiation. Cells that have decreased levels of differentiation are more radiosensitive than specialized cells.

Fractionation Instead of a single treatment consisting of a high dose, fractionation divides the dose to be delivered over a period of time, usually 6-8 weeks. At low doses of radiation, normal cells have an increased survival rate because of their ability to repair sublethal damage before the next fraction of radiation is delivered. Tumor cells do not possess the repair enzymes necessary to keep up with the repairs and as a result the cell is overwhelmed. http://www.usoncology.com/CompanyInfo/PhotoLibrary.asp

References Leaver, D., Washington C.M. (2004) Principals and Practice of Radiation Therapy. Second Edition pp. 55-84 St Louis, Mosby Statkiewicz Sherer, M.A., Ritenour, E.R., Visconti, P.J. (2002) Radiation Protection in Medical Radiography. Fourth Edition, pp85-154, St. Louis, Mosby. Ott, M.E. (2006, April 12) Radiation and why it is bad for humans. A videotaped lecture describing Radiation Types, Effects & Sources http://video.google.com/videoplay?docid=-1764500297917980309&q=radiation Gwozdz, J. T. (2002, July 20). IMRT - Intensity Modulated Radiation Therapy. A powerpoint presentation of IMRT Intensity Modulated Radiation Therapy. http://drjohng.com/Talk/IMRT/Slide1_GIF.html Low Dose Radiobiology Slideshows (n.d.) http://lowdose.tricity.wsu.edu/radiobio_slideshows.htm

References Radiation Therapy. (2003, February). Merck Research Laboratories http://www.merck.com/mmhe/au/print/sec15/ch182/ch182c.html) How Radiation Therapy Works. (n.d.) Physics Students Web Project of How Radiation Therapy Works http://www.unc.edu/~taleb84/phys25/therapy.html Großmann, V. (2004). Radiation Biology and Nanodosimetry http://www.ptb.de/en/publikationen/jahresberichte/jb2004/nachrdjahres/s22e.html Medical Physics. (2004). from Johns Hopkins University. http://www.radonc.jhmi.edu/html/medical_physics.html Radiation Therapy (n.d.) from Wikipedia. http://en.wikipedia.org/wiki/Radiation_therapy#How_it_works

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