6th radiobiology- cell survival curves

6th radiobiology- cell survival curves

• 1.
  Radiobiology- Cell Survival Curves Presenter: Dr. Gowtham Manimaran Moderator : Dr. Deepak Mittal
• 2.
  Contents • What isa cell survival curve? • In Vitro Cell survival curve • Linear quadratic model • Mechanisms of cell killing
• 3.
  Cell Survival curve •It is a relationship between the radiation dose and the proportion of cells that survive. • To understand this ,it is mandatory to define Cell death 1. For differentiated cells – loss of specific function 2. Proliferating cells – loss of capacity for sustained proliferation Clonogenic cell – A survivor that has retained its reproductive integrity and is able to proliferate to produce a colony.
• 4.
  In Vitro CellSurvival Curve • With modern techniques , single cell suspension by the use of enzyme trypsin is made and grown into what is called as established cell lines. • Plating efficiency indicates the percentage of cells seeded that grow into colonies. • Surviving fraction: Colonies counted / [Cells seeded × (PE / 100)] A: In this unirradiated control dish, There are 70 colonies; therefore, the plating efficiency is 70%. B: Two thousand cells were seeded and then exposed to 8 Gy of x- rays. There are 32 colonies on the dish. : surviving fraction 32 / (2,000 × 0.7)= 0.023
• 5.
  • The cellculture technique is used to generate a cell survival curve. • But it is not adequate to think there there is only a linear relation between dose a radiation and the cell changes. Radiation is believed to affect the organism as a whole. • Recently, interest has been renewed in other effects of radiation like radiation- induced vascular changes, bystander effects, and immune cell infiltration into normal tissues and tumors.
• 6.
  Random nature ofcell killing • It is given by Poisson statistics - indicate that if 100 lethal lesions are distributed randomly throughout 100 equally radio-sensitive cells, 37 cells will be spared • A dose of radiation that induces an average of one lethal event per cell leaves 37% of irradiated cells still viable; this is called the D0
• 7.
  • For mammaliancells, the x-ray D0 usually lies between 1 and 2 Gy. • The number and type of DNA lesions per cell detected immediately after a dose of 1 Gy of x-rays is approximately: Double-strand breaks (DSBs) 40 – Responsible for cell killing, carcinogenesis, mutation. Single-strand breaks (SSBs) 1,000 Base damage >2,000 DNA-DNA crosslinks 30
• 8.
  Mammalian Cell Survival Curve
• 9.
  Linear Quadratic Model •The linear – quadratic model (LQ) was developed by Douglas and Fowler in 1972 [2], it was assumed that cell death due to ionizing radiation has two components: linear component (αD), directly proportional to dose, D, characterized by linear coefficient, α, corresponding to the cells that cannot repair themselves after one radiation hit and it is important for high-LET radiation and quadratic component (βD2 ) directly proportional to the square of dose characterized by the quadratic coefficient, corresponding to cells that stop dividing after more than one radiation hit, but can repair the damage caused by the radiation and it is important for low-LET radiation. The linear coefficient, α indicates the intrinsic cell radiosensitivity, and it is the natural logarithm (log e) of the proportion of cells that die or will die due to their incapacity to repair radiation- induced damage of ionizing radiation. The quadratic coefficient, β shows cell repair mechanisms, and it is the natural logarithm of the proportion of repairable cells due to their ability to repair the radiation-induced effect of ionizing radiation. In order to formulate equivalent fractionation schemes, to get information on acute and late responses and also to calculate additional doses after breaks from radiotherapy the LQ model is used. The early – and late-responding tissues distinction is very important as a result of the recognition that time–dose relationships are systematically different between them. The α/β ratio is dose for which the number of acutely responding cell deaths is equal to the number of late-responding cell deaths (the dose for which the linear and quadratic components of cell death are equal). For tumors and acute effects 3 Clinical application of linear-quadratic model 787 response in normal tissues, the mean α/β ratio is 10Gy [range 7– 20 Gy]. For late effects in normal tissues, α/β ratio range from 0.5 to 6 Gy [3]; the α/β ratio is not constant, may differ among tumor types and its value should be carefully chosen [3].