Radiation Biology for Physical Scientists/Radiation Interaction - Physical and Chemical Events

Energy Deposition in Biological Materials
The energy from radiation needs to be deposited into the cells of biological material before it can produce a biological effect. Charged particle radiation such as alpha particles, electrons and protons directly transfer their energy to other charged particles in cells through Coulomb Interaction. However, uncharged radiation such as x-rays, gamma rays and neutrons cannot directly transfer their energy. Instead, they indirectly transfer all (Photoelectic Effect) or a portion of their energy (Compton Effect) to charged particles in the cells and these charged particles transfer their energy to the biological material through Coulomb Interaction. The units for the energy deposited is Joules per kilogram which is given a special name of Gray in honour of English scientist Louis Harold Gray.

Excitation and Ionization
The energy deposition can lead to two different events that are dependent on the amount of energy absorbed by the cells.

One type of event is called excitation where the orbital electrons of atoms in the cells get enough energy to make an atomic transit from the ground state to a higher energy level, without leaving the atom. This type of event will not be the focus of this book. The second type of event is called ionization which happens when one or more orbital electrons from an atom in the cell has enough energy to leave the atom leading to ion pairs. Ionization radiation can be further reclassified as directly ionizing and indirectly ionizing depending on the source of the energy.

Ionization Density
Ionization from radiation in biological material leads to a random and uneven distribution of deposited energy in cells. The spatial distribution of the energy imparted by the charged particle is quantified by the Linear Energy Transfer (LET) metric. It is the quotient of the average energy imparted and the distance traversed by the radiation with units of keV/μm.

Radiation can be reclassified into low LET or high LET radiation based on their LET value. The demarcation value between low and high LET is about 10 keV/μm.

Direct and Indirect Action
Cells contain organic compounds (proteins, carbohydrates, nucleic acids and lipids), as well as, inorganic compounds (minerals) dissolved or suspended in water. The critical target within the cell for damage from radiation is DNA; however damage to other sites in the cell may lead to cell death. The biological effect of radiation can be classified based on the atoms or or molecules in the cell that are ionized by radiation. Direct Action of radiation refers to the ionization of critical target atoms or molecules in the cell such as DNA. Indirect Action refers to the ionization of atoms of molecules in a cell other than target atoms and molecules. In biological material, the ionization of water (Radiolysis) is important since more than 80% of a cell's mass is water. Direct Action is the dominant process in the interaction of high LET particles because it results in a denser column of radiation that is more likely to interact directly with DNA. Sparsely ionizing radiation such as low LET particles dominantly interact by indirect action.

Chemical Events
The average energy dissipated in an ionization event is 33eV which is more than enough to break chemical bonds in the atoms and molecules of cells. The typical energy needed to break the bond in the DNA bases is 9eV. Breaking these chemical bonds causes a chain of chemical events that produces free radicals leading to biological damage. A radical is an atom or molecule that possesses an unpaired electron in its outer shell which usually makes it highly chemically reactive. A free radical is a radical which is able to diffuse from the site it was produced prior to interacting with another molecule.

Direct Action
Radiation ionizes a target molecule and forms a positively charged radical on the molecule. The letter R is a placeholder for a hydrocarbon group side chain.

RH + radiation → RH•+ + e-

The RH•+ cation radical decomposes into a sugar or base radical and hydrogen cation.

RH•+ + e- → R• + H+

Chemical reactions with this radical leads to breaks in one or both strands of the DNA helix. These single and double strand breaks will be discussed further in the next chapter.

Indirect Action
Ionization of water causes it to lose an electron and produces a positively charged ion radical H2O+• and a free electron e-. Through a chain of chemical reactions, H2O+• and e- generate highly reactive free radicals such as the hydroxyl radical (OH•) and H•

H2O + radiation → H2O+ + e-

H2O+ H2O → H3O+ + OH•

These free radicals can diffuse to the target molecule leading to DNA or sugar radicals that eventually produce single and double strand breaks of the DNA helix.

RH + OH• → R• + H2O

The highly reactive hydroxyl radical (OH•) and is believed to be responsible for more than 2/3 of mammalian cell damage. Radiation protection drugs typically work by scavenging free radicals. These drugs are generally less effective for high LET radiation since direct action dominates.