Radiobiology and Physics in Cancer Treatment

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Radiobiology and Physics in Cancer Treatment

  1. 1. Radiobiology and Physics inRadiobiology and Physics in Cancer TreatmentCancer Treatment Dr. Vic MontemayorDr. Vic Montemayor Department of Physics & AstronomyDepartment of Physics & Astronomy Middle Tennessee State UniversityMiddle Tennessee State University An Introduction to PHYS 3600An Introduction to PHYS 3600
  2. 2. History: Discovery of X-rays Wilhelm Röntgen: 1895 Timeline of Events: • 1896: first radiograph • 1896: first medical application • 1897: first therapeutic use
  3. 3. First Radiograph (1896)
  4. 4. 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
  5. 5. Radiobiology Radiobiology: the study of the effects of ionizing radiation on living tissue Ionizing 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)
  6. 6. Radiobiology Types of Ionizing Radiation: 1. Electromagnetic Radiation x-rays, gamma rays
  7. 7. Radiobiology Types of Ionizing Radiation: 2. Particles charged: electrons, protons, α particles, heavy nuclei uncharged: neutrons
  8. 8. Critical Target of Radiation Treatment DNA! The biological effects caused by radiation result primarily from damage to the DNA.
  9. 9. 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
  10. 10. 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
  11. 11. Direct Action of Photons • incident photon releases energetic electron that then produces an effect in DNA
  12. 12. 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×
  13. 13. Production of Biological Effects incident photon results 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 O H O OH + + + ×→ +10 10 s− τ →:
  14. 14. Time Scale for Biological Effects cell killing hours to days (when damaged cell tries to divide) oncogenic overt cancer may not appear for 40 years or more mutation resulting in inheritable changes may take up to many generations
  15. 15. 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↔ ↔
  16. 16. 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)
  17. 17. The Cell Cycle Teachline, The Hebrew University of Jerusalem (Alexander Silberman Institute of Life Sciences) HamsterHamster Cells (h)Cells (h) HeLa CellsHeLa Cells (h)(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
  18. 18. 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)
  19. 19. Generic Cell Survival Curves
  20. 20. 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
  21. 21. 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.)
  22. 22. Cancer Treatment Modalities using Radiation − brachytherapy uses radioactive “seeds” − radiation therapy using photon or charged particle beams
  23. 23. Cancer Treatment Modalities using Radiation − brachytherapy uses radioactive “seeds” − radiation therapy using photon or charged particle beams
  24. 24. Welcome...!

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