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Similar a FOUR R’S OF RADIOBIOLOGY.ppt(20)



  3. Efficacy of fractionation based on radiobiological experiments and clinical evidence is expressed in terms of FOUR Rs of radiobiology. Fractionation of dose spares normal tissues because of repair of sublethal damage between dose fractions and repopulation of cells if the overall time is sufficiently long. At the same time, it increases damage to the tumour because of reoxygenation and reassortment of cells into radiosensitive phases of cell cycle between the fractions.
  5. REPAIR Radiation damage to mammalian cells can operationally be divided into three categories: 1. Lethal damage 2. Potentially lethal damage (PLD), 3. Sublethal damage (SLD), Base damage, Single-strand breaks (SSBs), Double-strand breaks (DSBs),
  6. DNA REPAIR PATHWAYS Base Excision Repair Nucleotide Excision Repair DNA Double-Strand Break Repair ◦ Nonhomologous End-Joining ◦ Homologous Recombination Repair Crosslink Repair Mismatch Repair
  7. SUBLETHAL DAMAGE REPAIR By double strand break repair. Homologous recombination repair Requires an undamaged DNA strand as a template. Error free process Late S/G2 phase Non homologous recombination repair End to end joining. Error prone, responsibility for premuagenic lesions G1 phase.
  8. SIGNIFICANCE OF SUBLETHAL DEMAGE REPAIR. Tends to improve cell survival. Repair occurs during intervals of fractions. Needs 2 hour interval for maximum effect.
  9. Cell survival curves
  10.  The single dose survival curve for most cells has a finite initial slope apparently due to a (single-hit) non-repairable damage component ,so there is a limit below which further reduction of the fraction size will no longer reduce the effective slope of the survival curve.  At this limit, essentially all the repairable damage is being repaired between each fraction so that the cell killing is due almost entirely to non-repairable events.
  11. Redistribution  If an asynchronous population of cells present in different phases of cell cycle is exposed to a large dose of radiation, more cells are killed in the sensitive than in the resistant phases of the cell cycle. The surviving population of cells progresses around cell cycle and said to be partly synchronised.  In 6 hrs. S (resistant) to G2-M (sensitive) phase.
  12. Repopulation  It is the Increase in cell division that is seen in normal and malignant cells at some point after radiation is delivered.  In normal tissues, repopulation occurs in different speeds depending on the tissue.  Early responding tissues begin repopulation at about 4 weeks.  Late responding tissue only begin repopulation after a conventional course of radiation has been completed and therefore repopulation has minimal effect on these tissues.
  13. ACCELERATED REPOPULATION Treatment with any cytotoxic agents, including radiation, can trigger surviving cells (clonogens) in a tumor to divide faster than before. This is known as accelerated repopulation.
  14. For the oxygen effect to be observed, oxygen must be present during the radiation exposure or, to be precise, during or within microseconds after the radiation exposure. The absorption of radiation leads to the production of fast-charged particles. The charged particles, in passing through the biologic material, produce several ion pairs. very short life spans (about 10-10 second) The free radicals are important because although their life spans are only about 10-5 second, that is appreciably longer than that of the ion pairs.
  15. Cells are much more sensitive to x-rays in the presence of molecular oxygen than in its absence (i.e., under hypoxia). The ratio of doses under hypoxic to aerated conditions necessary to produce the same level of cell killing is called the oxygen enhancement ratio (OER). It has a value close to 3.5 at high doses (A), but may have a lower value of about 2.5 at x-ray doses less than about 2 to 3 Gy (B) Tumor Hypoxia
  16. Chronic hypoxia Results from the limited diffusion distance of oxygen through tissue that is respiring. The distance to which oxygen can diffuse is largely limited by the rapid rate at which it is metabolized by respiring tumor cells. Many tumor cells may remain hypoxic for long periods.
  17. Acute hypoxia Is the result of the temporary closing of a tumor blood vessel owing to the malformed vasculature of the tumor. Tumor vasculature lacks smooth muscle and often has an incomplete endothelial lining and basement membrane.
  19. SIGNIFICANCE OF REOXYGENATION If all the human tumors reoxygenate rapidly, use of multifraction course of radiotherapy, extending over a period of time can deal effectively with any hypoxic cells of human tumors.
  20. 5th R OF RADIOBIOLOGY Radiosensitivity of the living tissues varies with maturation & metabolism. Radiosensitive cells are- Stem cells Younger tissues High metabolic activity High proiferation and growth rate
  21. Response of tissue is determined by amount of energy deposited per unit mass(dose in Gy). Physical Factors linear energy transfer relative biologic effectiveness fractionation. Biological Factors AGE oxygen effect recovery chemical agents Two identical doses may not produce identical responses due to other modifying factors
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