Radiobiology > Biologic Interactions > Modifers of Cell Sensitivity > Sensitizers


Sensitizers to Radiation-induced Damage

Chemical modifiers of cell sensitivity

Chemical and pharmacological agents have been discovered that modify the biological effect of X-rays. The most dramatic of these is OXYGEN.

The Oxygen Enhancement Ratio (OER) reflects the increased number of reactive free radicals (leading to increased indirect damage) generated in the presence of oxygen in irradiated tissues. Please note: this phenomenon is valid only for low LET radiation (i.e. cannot be demonstrated for particles with LET >150 KeV per micron).

  • The OER for most mammalian cells is 2.3-3.0

Thus, in the absence of molecular oxygen, the dose of X-rays to produce the same degree of cell-killing as under well-oxygenated conditions would need to be increased by a factor of about 3.

What are clinical consequences of this oxygen effect?

  • Hyperbaric oxygen can potentate damage by oxygenating hypoxic foci within tumors.
  • Likewise, local hypoxia (created through use of a tourniquet or local vasoconstrictor medication) can protect irradiated tissues.

Other Chemical Sensitizers: Oxygen mimics

Pharmacologic agents that may penetrate hypoxic centers of tumors and serve to increase tumor cell sensitivity to radiation effects similar to oxygen have been identified. Metronidazole and the Nitrofurans class of pharmacologic compounds are examples. In vivo support for their effectiveness is limited, however.


Cell cycle selectors

  • Actinomycin-D
  • Hydroxyurea
  • Methotrexate
  • 5-flurouracil

The compounds listed have greater specific toxicity for cells in S-phase (i.e., they are anti-metabolites). Any asynchronous population of cells treated with these medications will appear to have greater radiosensitivity, as survivors of the drug treatment are more likely to be in the more radio-sensitive G1, M, or G2-phases of the cell cycle.

By contrast to these agents, halogenated pyrimidines may be regarded as true sensitizers. For example, incorporation of BUdR into DNA in place of thymidine thwarts a cellís ability to undertake sub-lethal repair.


Hyperthermia

Tumor cells in general are more sensitive to thermal damage than normal cells. Cells subjected to thermal stress (43 C for 30-60 minutes) are more sensitive to radiation injury than non-heated cells. Dose-modifying factors of 2-10 have been reported.




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