Molecular Effects of Radiation and Their Modifiers

1. Radiation-Induced Damage: Direct vs. Indirect Action

Radiation-induced damage to biological targets can occur through two primary mechanisms: direct action and indirect action. These actions involve different processes at the molecular level that ultimately result in observable biological damage.

2. Direct Action of Radiation

Direct action refers to the ionization or excitation of atoms in the biological target, leading to a cascade of events that eventually cause macroscopic damage. In mammalian cells that are normally oxygenated, direct action accounts for about one third of the radiation-induced damage when exposed to low Linear Energy Transfer (LET) radiations, such as electrons and photons.

• Mechanism: Ionization or excitation via Coulomb interactions with the atoms of the biological target.
• Contribution: Direct action is responsible for about 1/3 of the damage in normoxic conditions for low LET radiation.
• Effect: Leads to damage at the atomic and molecular level in the exposed cells, potentially resulting in mutations or cell death.

3. Indirect Action of Radiation

Indirect action primarily involves the ionization or excitation of water molecules, which are abundant in the cellular environment. The resulting free radicals then migrate and cause damage to the biological target. This mechanism accounts for the majority of radiation-induced damage, especially in normoxic cells, where it is responsible for about two-thirds of the total damage.

• Mechanism: Ionization or excitation of water molecules leads to the production of free radicals (e.g., hydroxyl radicals, H₂O^*). These radicals can damage nearby biological molecules.
• Contribution: Indirect action is the main cause of radiation damage, especially with low LET radiations.
• Effect: Damage may include strand breaks in DNA, oxidation of lipids and proteins, and disruption of cellular functions.