Question

Sketch 2 curves on the same graph for mammalian cells: after X-rays and after alpha-particles irradiation. Explain quantitatively the dependence on radiation dose of the survival for X-ray curve at low doses (up to 0.5Gy), at very high doses (higher than 7Gy). Discuss the mechanisms involved in cell death

Answer 1

Cell death-Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, or may result from such factors as disease, localized injury, or the death of the organism of which the cells are part. It is loss of cells as an individual ages through pathology or perhaps reasons that cannot be attributed to any specific abnormality other than the passage of time. This loss is most critical in the immune system, because it leads to substantial increase in susceptibility to infection; in the central nervous system (CNS), because lost neurons are currently irreplaceable.

Programmed cell death (or PCD) is cell death mediated by an intra-cellular program. PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle.

Apoptosis-- It is the process of PCD that occur in multicellular organism.Biochemical events lead to characteristic cell changes and death. cells are induced to positively commit suicide whilst in a homeostatic context; the absence of certain survival factors may provide the impetus for suicide.

Autophagy - It is cytoplasmic, characterized by the formation of large vacuoles that eat away organelles in a specific sequence prior to the destruction of the nucleus.

Cell-survival curves are used to describe the relationship between radiation dose and the proportion of cells that survive. Mathematical models are used to describe cell survival data. Survival of normal cells is an important consideration in radiation therapy. It is the therapist’s aim to destroy cancer cells while protecting normal cells to the greatest extent possible.

Cell survival curves have a characteristic shape when plotted on a log-linear scale with radiation dose on the x-axis and the log of cell survival on the y-axis. At low doses, the curve tends to be straight (linear). As the dose increases, the curve bends over a region of several Gy; this region is often referred to as the shoulder of the survival curve. At very high doses, the curve tends to straighten out again.

Many biophysical models have been proposed to mathematically capture this relationship between radiation dose and cell survival. The most commonly used model is the LQ model, which assumes that there are two components to cell killing: one that is proportional to the radiation dose and another that is proportional to the square of the dose. Cell survival in this model is represented by the following exponential function:

  S(D)= exp{-(αD+βD^2)}

where S is the fraction of cells surviving a dose, D; e is the mathematical constant approximately equal to 2.71828; and α and β are constants that represent the linear and quadratic components of cell killing, respectively. At dose D = α/β, the contributions from the linear and quadratic components of cell killing are equal.

The LQ model is convenient in that it depends on only two parameters (α and β) and it is relatively easy to manipulate mathematically.