https://www-pub.iaea.org/MTCD/Publications/PDF/TCS-42_web.pdf

theory-of-radiation-to-cell-death cell-survival-curves

Biological effects of radiation

Biological effects of radiation result from high-energy particles breaking DNA double-stands and chromosome damage resulting in

  • acute (early) and/or chronic
  • mild (skin irritation) or severe

Effects depend on type of radiation, total dose, dose rate, cell type and cell environment

Stochastic effects of radiation = low dose of radiation can lead to permanent modifications in functioning of some cells with long delayed effects of radiation such as genetic changes or the induction of cancer

Deterministic effects of radiation = high dose of radiation can lead to microscopically observable damage with death of individual cells and radiation sickness which can lead to death

Boron Neutron Capture Therapy (BNCT)

A targeted, binary radiotherapy that kills cancer cells by inducing a localized nuclear reaction, sparing healthy tissue.

  • compounds enriched with boron-10 are administrated prior to irradiation
  • the boron compound is irradiated with thermal neutron beams, releasing high energy alpha particles (He)
  • used for difficult-to-treat, invasive cancers

Radiation interaction with water

Water is the most predominant molecule in living organisms (80% of the mass of a living cell). Therefore, a major proportion of radiation energy deposited will be absorbed in cellular water.

  1. Interaction with radiation with water causes ionization and excitation producing radical-cations and free electrons.
H_{2}O + IR \to H_{2}O^{+} + e^{-} \\ H_{2}O^{+} \to H^+ + OH^{*} \end{align}$$ 2. water molecules react with the free electron to form a hydroxy ion $$e^- + H_{2}O \to H_{2}O^- \to OH^- + H^{*}$$ So the ultimate result is the formation of an ion pair ($H^+ , OH^{-}$) and free radicals ($H^* , OH^*$) **Free radicals** have an unpaired electron in their outer shell, a state which confers to a high degree of activity. Free radicals initiate chemical reactions that lead to the production of damage via indirect action in the cell. So summary of interaction of radiation with water = $$\text{x-ray photon} \to \text{fast electron} \to \text{ ion radical} \to \text{free radical} \to \text{chemical changes} \to \text{biological effect}$$ ### Direct and indirect action of ionizing radiation **Indirect action** = when ionizing radiation interacts with water molecules creating highly reactive free radicals which then cause biological effects - uncharged particle $\to$ charged particle $\to$ deposited dose **Direct action =** when ionization and excitations are produce directly in critical biological macromolecules (e.g. DNA) - charged particle $\to$ deposited dose ### Dose response relationship - At low radiation dose, both DNA breaks that lead to a lethal chromosome aberration are often produced by a single charged particle track (one radiation interaction). So, the probability of forming a lethal aberration increases linearly with dose - At higher dose, the two DNA breaks that combine to form an exchange aberration can arise from two independent radiation tracks. So, the the probability of an interaction is then proportional to the square of the dose ### Cell cycle The cell cycle can be divided into two periods: - Interphase = cells are growing, replicating, performing function - M-phase = mitosis where cells are actively dividing cells are most radiosensitive in M and G2 phase, and the most radioresistant in late S phase.