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The action of ionising radiation in living tissue takes place in three phases:

Physical phase

It lasts a very short period of time, in the order of 10^-13 second. It is characterised by the ionisations and molecular excitations following the energy deposit during the crossing of the beam.

Physicochemical phase

It lasts from a few seconds to a few minutes. The ionised and excited molecules react between each other and with neighbouring molecules.

Generally, we distinguish between the direct effect in relation to direct impact of the beam on cellular macromolecules, in particular DNA, and the indirect effect in relation to macromolecule modifications provoked by free radicals originating from water radiolysis. These indirect effects are the major component (70-80%) of beam impact on living tissue.

A few explanations are given in specific pages on physicochemical effects and on water radiolysis.

In the presence of oxygen, specific radicals are created with a strong oxidising power interacting with water to induce the formation of hydrogen peroxide which is a strong oxidising molecule. The 'oxygen effect' is observed in radiobiology with an increased radiosensitivity of well oxygenated cells compared to hypoxic cells.

Biological phase

Either by direct or indirect effect, ionising radiation alters the structure of macromolecules, thus disrupting the main functions of cellular life.

Action on nuclear acids

DNA is the elective target of ionising radiation. When the cytoplasm and the nucleus of a cell are selectively irradiated, cellular death occurs with much lower doses and more often when irradiation attacks the nucleus: lethal cellular lesions are those which concern DNA (see the diagram).

The main lesions are:

• most often single strand breaks without gap, by rupture of diester links. These breaks are generally not lethal since DNA repair can be made by a ligase in 2 to 10 minutes,
  
• more rarely, single strand breaks with gap, by the disappearance of a sugar or DBA base: the repair time is longer since it requires the action of both a polymerase and a ligase,
  
• occasionally, base alterations, which are non lethal lesions, but which can be the source of mutation if the lesion is not repaired or is repaired inaccurately. Eighty percent of theses lesions are repaired within 15 minutes by excision-synthesis mechanisms which require endonucleases, glycolases, polymerases and ligases,
  
• finally, double strand breaks which result from simultaneous events on the two strands or from two independent single break lesions. Every double strand break is lethal if not repaired and the number of induced double strand breaks induces the cellular radiosensitivity of a tissue.

The capacity to repair double strand breaks depends on their nature: they are more difficult to repair if associated with a loss of chromosomal material, when links with proteins are created or if they are numerous and close to each other.

Generally, during irradiation, one double strand break occurs for 20 single strand breaks.

Action on proteins

Some radio-induced modifications of the protein structure may provoke physiological perturbations which can be lethal:

• alteration of membrane permeability (for instance: on ionic pumps),
  
• diminution of intercellular communication by perturbation of proteins constituting a gap junction,
  
• modification of the transmembrane signal transduction.

Action on lipids

Lipid peroxidations diminish membrane fluidity inducing alterations in cell membrane functions.