9/28 Rad Bio CH4

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9/28 Rad Bio CH4
2012-09-25 16:05:39
rad science radiation biology therapy

9/28 Rad Bio
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  1. What types of ionizing radiation are High LET
    Protons & Alpha Particles are High LET

    High LET causes direct action on a cell.
  2. What types of ionizing radiation are Low LET
    X-Rays & Gamma Rays are low LET

    Low LET causes indirect action on a cell (ricochet)
  3. What percentage of single breaks heal by restitution?
    95% of all single breaks heals by restitution.
  4. What are the most radiosensitive cell phases?
    • G-2 is the most sensitive
    • M is the second most sensitive
  5. Which is the fastest phase?
    The M (mitosis) Phase is the fastest phase
  6. What are the building blocks of life?
    Proteins are the building blocks of life
  7. What contains an unpaired electron in the outer shell?
    Free Radical contains an unpaired electron in its outer shell, thus making it highly reactive.
  8. Anaplastic
    Anaplastic = Undifferentiated
  9. Tumors that originate from the epithelium?
    Carcinomas originate from the epithelium
  10. Tumors that originate from mesenchymal cells?
    Sarcomas originate from the mesenchymal cells
  11. Tumors of glandular tissue
    Adenocarcinomas originate from gladular tissue
  12. Phase of cell division when DNA is replicated
    S Phase is when DNA is replicated
  13. The phase characterized by rapid growth and active metabolism;
    The phase in which the cell synthesizes the necessary RNA and protein to carry out the function of the cell;
    Extremely variable in length
    G-1 phase
  14. The phase during which nuclear DNA is synthesized & chromosomes are duplicated
    • Synthesis 
    • S Phase
  15. The phase in which the cell prepares for actual division.

    Commences after DNA synthesis & continues until the cell begins to divide
    G-2 Phase

    G-2 is the most radiosensitive!
  16. The phase of division
    The shortest phase
    M Phase

    Mitosis Phase
  17. The process in which enzymes in the cell nucleus facilitates the transfer of information from a strand of DNA to a strand of RNA
  18. When the incoming radiation ejects an elctron from the shell of an atom, thus causing the atom to be charged
  19. When the electron from the outer shell of an atom is said to be excited but is not ejected from the shell
  20. R.B.E.
    Relative Biologic Effect (RBE)

    Relates the ability of radiations with different LETs delivered under the same conditions to produce the same result
  21. When ionizing radiation interacts with or near a key molecule, the sensitive area is termed a                     and an ionization event in this area is termed a                .
    When ionizing radiation interacts with or near a key molecule, the sensitive area is termed a target and an ionization event in this area is termed a hit.
  22. A chromosome aberration occurs when radiation is administered to cells in the           phase
    A chromosome aberration occurs when radiation is administered to cells in the G-1 phase or before the cell replicates its DNA in the S phase
  23. Mitotic Phase in which:
    1 Chromosomes shorten & thicken
    2 Centrioles move to opposite poles; Spindle fibers appear & orient between opposing poles
    3 Nucleoli & nuclear membrane disappear
  24. Mitotic Phase in which:
    Chromosomes align across equator of spindle fibers; 
    Each pair of chromatids is attached to spindle fiber at its centromere
  25. The Mitotic Phase in which
    1 Each centromere splits, thereby detaching 2 chromatids that compose each chromosome from each other.
    2 Sister chromatids move to opposite poles
  26. The Mitotic Phase in which:
    1 Essentially the reverse of prophase (DNA starts uncoiling)
    2 Nuclear envelope reappears, enclosing each new set of chromosomes
    3 Spindle fibers disappear
  27. Restitution
    The rejoining of chromosome fragments
  28. Chromosome aberration
    A chromosome aberration occurs when radiation is administered to cells in the G-1 phase or before the cell replicates its DNA in the S phase
  29. Chromatid Aberration
    • A chromatid aberration results when radiation is administered to cells in the G-2 Phase or after they have completed DNA synthesis.
    • Only one of the two daughter cells is affected if damage is not repaired
  30. Gross structural changes in chromosomes are referred to as:
    • Gross structural changes in chromosomes are referred to as aberrations
    • anomalies
    • lesions
  31. What is the result of radiation exposure to a cell in G-1 phase if restitution does not occur?
    Both fragments are replicated in the S phase, results in 4 fragments, each with a broken end
  32. A fragment that does not contain a centromere
    Acentric fragment
  33. Translocation
    Translocation is when the acentric fragment from one broken chromosome may join to a centromere-containing fragment of the other broken chromosome, thus forming a new normal appearing chromosome
  34. What are the consequences of radiation induced translocation?
    The consequences of radiation induced translocations can vary from no effect in somatic cells to malformed or nonviable offspring if translocation occurs in germ cells
  35. What are the major consequences of a double break?
    • The major consequences of a double break are
    • Deletions
    • &
    • Inversions
  36. Deletion
    Deletion of genetic material results when the fragments between the breaks is lost & the remaining two fragments join

    Effects depend on amount & significance of material lost
  37. Inversion
    • An Inversion of genetic material results when the middle fragment with two broken ends turns around or inverts before rejoining the other two fragments.
    • There is no loss of genetic material but gene sequences are affected
  38. What are the three categories of cellular response to radiation
    3 Categories of Cellular Response

    • 1 Division Delay
    • 2 Interphase Death
    • 3 Reproductive Failure
  39. Division Delay
    • Irradiated cells that involve a disruption in the mitotic index.
    • Result of Division (mitotic) Delay-
    • The cells in interphase at the time of RTx to be delayed in the G-2 phase
    • A decrease in the MI for the population (fewer cells divide)
  40. The                             the radiation dose, the                            the mitotic delay.
    The higher the radiation dose, the longer the mitotic delay & therefore the greater is the decrease in MI
  41. If doses are less than                     cGy, most cell lines recover & eventually proceed through mitosis.
    If doses are less than 1000 cGy, most cell lines recover and eventually proceed through mitosis.
  42. Mitotic Index
    • Mitotic Index (MI)
    • The ratio of the number of mitotic cells to the total number of cells in the irradiated population
  43. Reproductive Failure
    • Reproductive Failure (mitotic death) -most common cell response- A decrease in the reproductive integrity or cell's ability to under-go a limited number of divisions after irradiation
    • The effect on the reproductive capacity of cells can be traced to the extent of chromosome damage
  44. When do cells attempt to repair radiation damage?
    Cells attempt to repair radiation damage before mitosis by stopping in the G-2 phase to confirm that the DNA & proteins are intact. Any damage is repaired during this phase of the cell cycle so that it does not disrupt cell division or lead to possible cell death.
  45. Interphase Death
    • aka "non-mitosis" or " non-division" death 
    • The death of irradiated cells before these cells reach mitosis.

    If irradiated during G1, S, or G2 phase it results in interphase death.
  46. Mitotic Overshoot
    • Mitotic Overshoot
    • If the dose is less than 1000 cGy most cell lines recover & eventually proceed through mitosis.
    • This results in a higher than normal number of cells dividing
  47. Cellular Apoptosis
    • Cellular Apoptosis (Programmed Cell Death)
    • -unrelated to mitosis
    • -appears to have gene (p53 & bc/-2) involvement following exposure
    • -involves nuclear fragmentation, cell lysis & phagocytosis of the chromatin bodies by neighboring cellls
  48. Cell Suvival Curve
    • Cell survival curve  (Puck & Marcus)
    • A plot of the radiation dose administered on the x-axis versus the suviving fraction (SF) of cells on the y-axis
  49. Extrapolation Number
    Extrapolation number (n)

    the target number
  50. Quasithreshold Dose
    Quasithreshold Dose   (Dq)

    A measure of the cell's ability to accumulate & repair sub-lethal damage
  51. Dose
    Dose  (Do)

    A measure of radiosensitivity

    Radiosensitive cells have a low Do
  52. Multitarget Single Hit Model
    This equation accurately predicts the response of complex cell types, including most mammalian cells

    • log  n = Dq / Do
    •     e
  53. 3 Factors of conditional sensitivity
    3 Factors of Conditional Sensitivity:

    • 1 Physical
    • 2 Chemical 
    • 3 Biologic
  54. Conditional Sensitivity
    • The sensitivity of a cell to radiation can be modified.
    • Ancel & Vitemberger added to the laws of B&T- The environmental conditions of a cell before, during or after radiation exposure can influence the extent & appearance of radiation damage.
  55. Physical Factors that Influence Responce
    • Physical Factors-
    • -High LET vs Low LET

    • -Dose Rate
    •            Low dose rate less effective in damaging
  56. Chemical Factots that Influence Response
    • Chemical Factors-
    • -Radiosensitizers  (ie oxygen)
    •   enhance response
    • -Radioprotectors  (ie sulphydryls)
    •   decrease response
  57. How is the cell surivival curve different for oxic vs hypoxic cells?
    As the availability of oxygen decreases, cell response also decreases.

    Most pronounced with low LETs
  58. O.E.R.
    • Oxygen Enhancement Ration (OER)
    • The OER compares the response of cells with radiation in the presence & absence of oxygen
    • OER=             dose under hypoxic/anoxic conditions            
    •        Dose under oxic conditionsto produce same biologic effect
  59. D.R.F.
    • Dose Reduction Factor (DRF)
    • The ability of a radioprotector to diminish the effect of radiation
    • DRF=                      dose with protector                             
    •           dose w/o protector to produce equal biologic effect
  60. Radiosensitizers
    Enhance response of radiation

    • OXYGEN!!!!  
    • Halogenated Pyrimidines
    • Nitrimidazoles
  61. Radioprotectors
    • Decrease response of radiation
    • Sulphydryls        -known to cause side effects
    • Early examples: sodium cyanide, carbon moxide, epinephrine, histamine & serotonin because they all produce hypoxia in the cell
  62. Biologic Factors that Influence Response
    • Biologic Factors
    • -Position in the cell cycle

    -Ability to repair sub-lethal damage
  63. The Law of Bergonie and Tribondeau
    • The law of Bergonie & Tribondeau states that ionizing radiation is more effective against cells that are:
    • - actviely mitotic
    • - are undifferentiated
    • - have a long mitotic future
  64. According to the law of Bergonie & Tribondeau, which cells are the most sensitive?
    • Stem or Precursor Cells
    • According to the law of B & T, cells that are undifferentiated (ie, immature celles whose primary function is to divide & replace more mature cells lost from the population) are extremely radiosensitive.
  65. VIM Cells
    • Vegetative Intermitotic Cells (VIM)
    • Rapidly dividing, undifferentiated cells with a short life span      -ie. basal cells, crypt cells, erythroblasts & type A     spermatogenia
    • MOST radiosensitive
  66. DIM Cells
    • Differentiating Intermitotic Cells (DIM)
    • Actively mitotic, but a little more differentiated than VIM
    • - ie. type B spermatogenia
    • 2nd most radiosensitive
  67. Multipotential Connective Tissue Cells
    • Multipotential Connective Tissue Cells
    • Divide irregularly, more differentiated
    • -ie. endothelial cells of blood vessels & fibroblasts of connective tissue
    • Intermediate radiosensitivity
  68. RPM Cells
    • Reverting Post Mitotic Cells (RPM)
    • Do not divide, but are capable of doing so
    • Typically live longer, More differentiated
    • -ie. liver cells, mature lymphocytes
    • Relatively Radioresistant
  69. FPM Cells
    • Fixed Post Mitotic Cells (FPM)
    • Highly differentiated
    • Do not divide, may or may not be replaced upon death
    • -ie. certain nerve cells, muscle cells, spermatozoa, erythrocytes
    • Most Radioresistant
  70. What are the two compartments of tissue and organs?
    • PARANCHYMA - contains characteristic cells of that organ
    •     VIM, DIM, RPM, FPM, considered the functional unit of the cell
    • STROMA - consists of connective tissue & the vasculature
    •     intermediate radiosensitivity
  71. What is the radiosensitivity of an organ determined by?
    The radiosensitivity of a tissue or an organ is a function of the most sensitive cell it contains
  72. Regeneration
    • Regeneration refers to the replacement of damaged cells by the same cell type.
    • Results in partial to total rerversal of early radiation changes
    • Likely to occur in VIM & DIM cells
  73. Repair
    • Repair refers to the replacement of damaged cells by a different cell type, resulting in scar formation or fibrosis
    • More likely w/ high dose
    • Seen in RPM & FPM cells
  74. Acute Response to Radiation
    • Acute responses to radiation occur in less than 6 months.
    • Most common Acute or Early changes:
    • -Inflammation
    • -Edema
    • -Possible hemorrhaging in the exposed area
  75. Chronic Response to Radiation
    • Chronic changes occur after 6 months, not reversible
    • Most Common Chronic or Late Changes:
    • -Fibrosis
    • -Atrophy
    • -Ulceration
    • -Tissue Necrosis (most severe)
  76. RTOG
    Radiation Therapy Oncology Group

    Sets treatment standards