R9.2: Factors Influencing The Oxygen Effect

Physical Factors

Radiation quality has a major impact on the oxygen effect. Low-LET radiation relies on indirect DNA damage to cause its effect, through generation of free radicals which then interact with DNA. To make the DNA damage permanent, further reaction with oxygen is required to prevent repair. In the absence of oxygen, the indirect DNA damage is more readily repaired. High LET radiation causes direct damage by directly ionising DNA. This damage is not reliant on the presence of oxygen for permanency and therefore there is less change in cell kill in anoxic conditions.
Dose rate also has an impact on the oxygen effect. If oxic cells are killed by radiation, reoxygenation of hypoxic cells may also occur. If dose is delivered more slowly, it would follow that the previously hypoxic cells will become oxic during the treatment and therefore susceptiable to radiotherapy.
Fractionation of dose also exploits reoxygenation. If cells remained hypoxic then the expected cell kill would be much lower in a fractionated treatment. Instead, the curve closely follows the curve seen for a fully oxic cell population. Fractionation allows hypoxic cells to become oxic (either due to cell death or other dynamic processes) between fractions, making them susceptible to ongoing radiation.

Chemical Factors

The presence of oxygen is a chemical factor. Oxygen concentration may be increased by external (eg. hyperbaric oxygen) or internal methods (eg. blood transfusion to increase haemoglobin concentration).
Some evidence exists that the use of hypoxic cell sensitisers (eg. tirapazamine) may kill hypoxic cells preferentially. By combining these treatments with radiation the hypoxic cells may be targeted by a different method and lead to improved tumour control.

Biological Factors

If the patient suffers from chronic airways disease or other problems with oxygen transport (eg. anaemia) then oxygen concentration will be lower and the prevelance of hypoxic cells will be increased.

Technical Factors

These have minimal impact on the oxygen effect.