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Radiobiology and Radiobiology and Physics in Cancer Physics in Cancer
TreatmentTreatment
Dr. Vic MontemayorDr. Vic MontemayorDepartment of Physics & AstronomyDepartment of Physics & AstronomyMiddle Tennessee State UniversityMiddle Tennessee State University
An Introduction to An Introduction to PHYS 3600PHYS 3600
History: Discovery of X-rays
Wilhelm Röntgen: 1895
Timeline of Events:• 1896: first radiograph
• 1896: first medical application
• 1897: first therapeutic use
First Radiograph (1896)
Radioactivity
Timeline of Events:• 1898: discovered by Becquerel
• 1898: radium isolated by Pierre and Marie Curie
• 1901: first recorded intentional experiment in radiobiology performed by Pierre Curie
Radiobiology
Radiobiology: the study of the effects of ionizing radiation on living tissueIonizing radiation results in a localized absorption of a relatively large amount of energy in tissue.ave energy released in ionizing event in tissue
= 33 eV
typical chemical bond in tissue = 5 eV
(C=C bond energy = 4.9 eV)
Radiobiology
Types of Ionizing Radiation:
1. Electromagnetic Radiation
x-rays, gamma rays
Radiobiology
Types of Ionizing Radiation:
2. Particles
charged: electrons, protons, particles, heavy nuclei
uncharged: neutrons
Critical Target of Radiation Treatment
DNA!
The biological effects caused by radiation result primarily from damage to the DNA.
Two Categories of Ionizing Radiation
1. Directly Ionizing Radiation– has sufficient kinetic energy to change the atomic structure of the material through which it passes, thereby producing chemical and biological changes; charged particles are in this category
Two Categories of Ionizing Radiation
1. Directly Ionizing Radiation– has sufficient kinetic energy to change the atomic structure of the material through which it passes, thereby producing chemical and biological changes; charged particles are in this category
2. Indirectly Ionizing Radiation– does not produce chemical or biological damage directly, but rather gives up its energy in the release of energetic electrons that can then result in chemical and biological change; electromagnetic radiation is in this category
Direct Action of Photons
• incident photon releases energetic electron that then produces an effect in DNA
Indirect Action of Photons• incident photon
ionizes water molecule resulting in hydroxyl radical ( ) which diffuses to and interacts with DNA
About 2/3 of x-ray damage to DNA is caused by the hydroxyl radical!
OH
Production of Biological Effectsincident
photonresults in
ion radical (H2O+)
releases fast electron
chemical changes in DNA from broken bonds biological
effects resulting from damaged
DNA
production of hydroxyl radical
2 2
3
H O H OH O OH
1010 s
Time Scale for Biological Effects
cell killinghours to days (when damaged cell tries to
divide)
oncogenicovert cancer may not appear for 40 years or
more
mutation resulting in inheritable changes
may take up to many generations
Damage to DNA
• double strand breaks are thought to be the most important contribution to cell killing, mutation, or carcinogenesis
• single strand breaks are readily repaired
DNA bases :adenine thymine guanine cytosine
The Cell Cycle
Teachline, The Hebrew University of Jerusalem (Alexander Silberman Institute of Life Sciences)
Phases of the Cycle:•G1: growth and preparation of chromosomes for replication
• S: synthesis of DNA
• G2: preparation for mitosis
• M: the production of two separate cell nuclei (mitosis) and the subsequent pinching off of the cell membrane to produce two daughter cells (cytokinesis) (the M phase lasts about 1 h)
The Cell Cycle
Teachline, The Hebrew University of Jerusalem (Alexander Silberman Institute of Life Sciences)
Hamster Hamster Cells (h)Cells (h)
HeLa HeLa Cells (h)Cells (h)
MM 11 11
G1G1 11 1111
SS 66 88
G2G2 33 44
1111 2424
HeLa Cells: cervical cancer cells taken from Henrietta Lacks (died: 1951) forming an immortal cell line used in research
Measurement of Cell Survival
Cells are seeded in a dish and incubated for 7 days.A. 100 cells seeded; 70%
plating efficiency (70 colonies survive)
B. 2000 cells seeded and exposed to 8 Gy of x-rays (32 colonies survive)
Generic Cell Survival Curves
FYI: Mammalian vs. Microorganisms
A. mammalian cells
B. E. coli
C. E. coli B/r
D. yeast
E. phage staph E
F. B. megatherium
G. potato virus
H. Micrococcus radiodurans
Radiosensitivity with Cell-Cycle Phase
* time scales have been adjusted to that the S phase is comparable in both cell lines
General Characteristics:
• cells are most sensitive around M
• resistance is usually greatest in latter part of S
• for longer G1 phases, early resistance is followed by sensitive period
• G2 is about as sensitive as M
(This is studied using the mitotic harvest technique.)
Cancer Treatment Modalities using
Radiation− brachytherapy
uses radioactive “seeds”
− radiation therapy
using photon or charged particle beams
Cancer Treatment Modalities using
Radiation− brachytherapy
uses radioactive “seeds”
− radiation therapy
using photon or charged particle beams
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