Cell survival-curve

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Cell Survival Curve presentation. …

Cell Survival Curve presentation.
Ref: Radiobiology, Hall.
2012.01.126

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  • A cell still may be physically present and apparently intact, may be able to make proteins or synthesize DNAlost the capacity to divide indefinitely and produce a large number of progeny, it is by definition dead; it has not survived.
  • Talk about the radiation given.. Then incubated for a week or so.. Give an example …This process is repeated so that estimates of survival are obtained for a range of doses. 
  • Talk about the radiation given.. Then incubated for a week or so.. Give an example …This process is repeated so that estimates of survival are obtained for a range of doses. 
  •  “We will call him Quasimodo—he is almost a person!” Similarly, the quasithreshold dose is almost a threshold dose. 

Transcript

  • 1. Cell Survival Curves Abish Adhikari,Resident, Radiation/Oncology NAMS, Kathmandu
  • 2. Defination• “describes the relationship between the radiation dose and the proportion of cells that survive.”• Death could be either ‘Reproductive Death’ or ‘Functional Death’• ~100Gy is needed to ‘Destroy’ the cell, but only ~2Gy to functionally kill the cell.
  • 3. Survival• The capability of a cell to divide and form a colony is the sure sign of survival.• Tissue chopped → Trypsin → Single cell suspension → Electronic Counter• Cultivation → Incubation → Colonies Counting
  • 4. Some Formulae
  • 5. Some Formulae
  • 6. Shape of the Curve
  • 7. Shape of the Curve→ →
  • 8. Survival Curve• Dose plotted on a linear scale and surviving fraction on a logarithmic scale.• At High LETs, such as α-particles or low-energy neutrons, the curve is a straight line.• For sparsely ionizing (low LET) radiations, such as x-rays -
  • 9. Survival Curve• Starts out straight with a finite initial slope; that is, the surviving fraction is an exponential function of dose.• At higher doses, the curve bends.• At very high doses, the survival curve often tends to straighten again; the surviving fraction returns to being an exponential function of dose.
  • 10. Models of Description of the Curve• Single-target Model• Multi-target Model• Linear Quadratics Model
  • 11. Multi-Target Model• Described in terms of an initial slope, D1, resulting from single-event killing;• A final slope, D0, resulting from multiple-event killing;• And some quantity (either n or Dq) to represent the size or width of the shoulder of the curve.
  • 12. Multi Target Model• The quantities D1 and D0 are the reciprocals of the initial and final slopes.• It is the dose required to reduce the fraction of surviving cells to 37% of its previous value. 1 to 0.37 (i.e. to e-1)• For oxygenated mammalian cells, D0 is about 150 rads (1.5 Gy).• Dq defined as the dose at which the straight portion of the survival curve, extrapolated backward, cuts the dose axis drawn through a survival fraction of unity.
  • 13. three parameters,n, D0, and Dq, arerelated by theexpressionlogen = Dq/D0
  • 14. Linear-Quadratic Model• assumes that there are two components to cell killing by radiation,• one that is proportional to dose (Linear)• one that is proportional to the square of the dose. (Quadratic)
  • 15. • many chromosome aberrations are result of two separate breaks. Most of them lethal.
  • 16. Linear Quadratic Curve• The ‘bendiness’ is determined by α/β ratio• S = e-αD-βD2• S is the fraction of cells surviving a dose D,• α and β are constants.• If at a dose D, αD = βD2 then: D = α/β
  • 17. • SF = e-(αD+βD2)• D is the dose in Gy,• α is the cell kill per Gy of the initial linear component (on a log-linear plot) and• β the cell kill per Gy2 of the quadratic component of the survival curve.
  • 18. Survival curve for HeLa cells in culture exposed to x-rays.Characteristically, this cell line has a small initial shoulder
  • 19. Bystander Effect• Defined: “the induction of biologic effects in cells that are not directly traversed by a charged particle, but are in close proximity to cells that are.”• ~30% of bystander cells can be killed in this situation.• Presumably due to cytotoxic molecules released into the medium.
  • 20. Apoptotic and Mitotic Death• Greek word meaning “falling off,” as in petals from flowers or leaves from trees.• First, apoptosis after radiation seems commonly to be a p53-dependent process.• Mitotic death is common: Cells die attempting to divide because of damaged chromosomes.
  • 21. • -(α +α )D-β D2 S=e M A M• S is the fraction of cells surviving a dose D,• αM and αA describe the contributions to cell killing from mitotic and apoptotic death that are linear functions of dose,• βM describes the contribution to mitotic death that varies with the square of the dose.
  • 22. Extra-Radiosensitive• Ataxia telangiectasia (AT)• Basal cell nevoid syndrome• Cockaynes syndrome• Downs syndrome• Fanconis anemia• Gardners syndrome• Nijmegan breakage syndrome• Ushers syndrome
  • 23. EFFECTIVE SURVIVAL CURVE FOR A MULTIFRACTION REGIMEN• Multifraction regimens are used most often.• “If a radiation dose is delivered in a series of equal fractions, separated by sufficient time for repair of sublethal damage to occur between doses, the effective dose-survival curve becomes an exponential function of dose.” – thus making a straight line.
  • 24. • The biological effect (E) per fraction (n) of fractional dose (D) can be expressed as:• En = (αD+βD2)• So, Biologically Effective Dose BED = E/α = nD (1 + (D / (α/β)))
  • 25. • For calculation purposes, it is often useful to use the D10, the dose required to kill 90% of the population. For example:• D10 = 2.3 × D0 in which 2.3 is the natural logarithm of 10.
  • 26. Radiation & Micro-organisms 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. if radiation is used as a method of sterilization, 20,000 Gy necessary.