Mechanisms of Radiation Damage

Radiation Damage Mechanism

Objective

At the end of this presentation, you are expected to describe radiation cell damage mechanism (Direct and indirect ) and factors modifying radiation damage

Outline

• Basic Interaction of radiation with cell
• Linear energy transfer (LET)
• Relative Biological effect (RBE)

Factors Modifying Radiation Damage or Effect

Introduction

The biological effects of radiation result mainly from damage to the DNA, which is the most critical target within the cell; however, there are also other sites in the cell that, when damaged, may lead to cell death.

When ionizing radiation is absorbed in biological material, the damage to the cell may occur in 2 ways:

• Direct

Indirect

Direct

• IR
• 
• Chemical changes
• 
• Biologic effects
• Indirect
• IR fast electron (e) + H2O
• 
• free radicals
• 
• chemical changes
• 

biological effects

Direct and indirect actions of radiation on DNA

Direct Action

Radiation is directly deposited in the critical target, resulting in excitation or ionisation of the target More likely after HIGH LET radiation Produces damage by direct ionisation of a biological macromolecule

Indirect Action

In indirect action the radiation interacts with other molecules and atoms (mainly water, since about 80% of a cell is composed of water) within the cell to produce free radicals (hydroxyl), which can damage the critical target) within the cell.

About 2/3 of the biological damage by low LET radiations e.g. X rays or electrons is due to indirect action.

LINEAR ENERGY TRANSFER (LET)

Linear energy transfer (LET): is the mean amount of energy that a given ionizing radiation imparts to absorbing medium (such as tissue) per unit path length.

Used in radiobiology and radiation protection to specify the quality of an ionizing radiation beam

Types of Radiation according to LET

• There are two types of radiation in respect of linear energy transfer (LET)
• Low linear energy transfer radiation ( LOW LET radiation)

High linear energy transfer radiation ( HIGH LET radiation)

LOW LET radiation

• Are radiation that cause a sparsely ionization to the medium track
• Examples include
• X-ray radiation
• Gamma ray radiation

Electron radiation

HIGH LET radiation

• Are radiation that cause a densely ionization to the medium track
• Examples include
• Neutron radiation
• Proton radiation
• Alpha radiation

Other heavy particle radiation

Time scale of effects of radiation

• Physical
• Chemical

Biological

Factors Modifying Radiation Damage or Effect

Many factors influence or modify radiation damage and may alter radiation effectiveness or lead to unwanted side effects.

Factors

• The following factors may influence Radiation Damage
• Physical
• Chemical

Biological

1. Physical Factors

• Include;
• Type of radiation used
• Dose

Temperature

Physical Factors

Type of Radiation:

High LET (Linear Energy Transfer) radiation such as neutrons or α-particles will usually have a greater biological effect. This is due to increased cell killing as radiation induced damage is more closely spaced.

As LET increases over 100 keV/μm, cell killing decreases as the energy delivered exceeds that needed to kill the cell.

Physical Factors

Dose

Total dose is perhaps the most important physical factor. Very low doses are unlikely to lead to any visible response, whereas very high doses (single dose over 20 Gy) have the potential to kill most human cells.

Dose Rate at which dose is delivered will also impact on cell survival, as low dose rates allow for DNA repair to occur during radiation delivery. Very low dose rates may also allow reoxygenation or redistribution to occur.

Physical Factors

• Temperature:

Increased temperature leads to an increase in cell killing.

This is due to deficiency in DNA double strand break repair that occurs at higher temperatures.

Chemical Factors

• The oxygen effect refers to the increased cell killing in oxic conditions.

Anoxic cells are between 2 – 3 times more resistant to low LET radiation than oxic cells.

Therefore, the addition or reduction in oxygen will have effects on the radiation reaction.

Chemical Factors

Radiosensitisers, such as cisplatin or 5-fluorouracil, function by increasing the cellular damage caused by radiation.

The presence of these chemicals leads to an increase in the observed radiation effect.

Radioprotectors, such as amifostine, reduce the effect ionising radiation has on cells. This is often by increasing the availability of anti-oxidants which prevent ‘fixing’ of radiation damage

3. Biological Factors

Biological factors are due to the cell being irradiated or the organism. Include;

Type of cells example Haemopoietic differentiated cells typically respond to low doses of radiation, whereas well skin cells do not suffer ill consequences except at very high doses Cell cycle stage; Cells in S-phase are typically resistant, whereas those undergoing M-phase are generally much more radiosensitive.

Haemopoietic cells- immature cells that can develop into all types of blood cells including white blood cells red blood cells and platelets

Biological Factors

Age; Children are much more likely to suffer from secondary malignancies due to radiation exposure. Children also have developing tissues (such as cartilage) which can be permanently damaged by low doses of radiation (10 – 20 Gy).

Haemopoietic cells- immature cells that can develop into all types of blood cells including white blood cells red blood cells and platelets

Summary

Various group of factors influence radiation damage.

It is vital to aware of such factors as they may alter radiation effectiveness or lead to deleterious side effects.