prefinal-radbio

• Even though the initial interaction between radiation and tissue occurs at the electron level, observable human radiation injury results from change at the molecular level

  
• The occurrence of molecular lesions is identified by effects on macromolecules and on water
• The human body is an aqueous solution that contains 80% water molecules, radiation interaction with water is the principal molecular radiation interaction in the body
• The ultimate damage occurs to the target molecule, DNA, which controls cellular metabolism and reproduction
• The effect of irradiation of macromolecules is quite different from that of irradiation of water
• Even though the initial interaction between radiation and tissue occurs at the electron level, observable human radiation injury results from change at the molecular level
• The occurrence of molecular lesions is identified by effects on macromolecules and on water
• When macromolecules are irradiated in vitro, a considerable radiation dose is required to produce a measurable effect. Irradiation in vivo demonstrates that macromolecules are considerably more radiosensitive in their natural state
• Solution


  A liquid that contains dissolved substances. A mixture of fluids such as water and alcohol is also a solution
• Major effects when macromolecules are irradiated in solution in vitro

  • Main-chain scission
  • Cross-linking
  • Point lesion
• Main-chain scission


  The breakage of the backbone of the long-chain macromolecule, resulting in the reduction of a long, single molecule into many smaller molecules
• Main-chain scission reduces not only the size of the macromolecule but also the viscosity of the solution
• Viscosity


  The thickness and slowness of a fluid to flow, e.g. cold maple syrup has high viscosity, tap water has low viscosity
• Cross-linking


  The process where small, spurlike side structures on macromolecules attach to a neighbouring macromolecule or another segment of the same molecule, increasing the viscosity of the solution
• Point lesion


  The disruption of single chemical bonds in macromolecules, causing minor modifications that can lead to malfunction within the cell
• All these types of radiation effects on macromolecules are reversible through intracellular repair and recovery
• Macromolecular synthesis


  1. Molecular nutrients are brought to the cell, broken down (catabolism) to release energy, which is then used to synthesize macromolecules (anabolism)

  2. Proteins are manufactured by translation of the genetic code from transfer RNA, which had been transferred from messenger RNA (mRNA), which was transcribed from DNA
• Radiation damage to any of these macromolecules may result in cell death or late stochastic effects
• Proteins


  • Continuously synthesized throughout the cell cycle, occur in much more abundance than nucleic acids, so are less radiosensitive than nucleic acids
• DNA


  • Not as abundant as proteins or RNA, so more radiosensitive
• DNA synthesis


  1. During G1 phase, deoxyribose, phosphate, and base molecules accumulate in the nucleus in the double-helix form

  2. In S phase, the DNA ladder opens up and the single strands are replicated, forming two identical daughter DNA molecules
• Deterministic effect


  DNA damage without visible chromosome aberration can lead to cell death and tissue/organ destruction

  
• Stochastic effect


  DNA damage can result in abnormal metabolic activity and uncontrolled rapid proliferation of cells, leading to radiation-induced malignant disease

  
• Genetic effect


  DNA damage in germ cells can be passed on to the next generation, with characteristics of a stochastic effect
• Although each of these DNA effects results in a structural change, they are all reversible
• Radiation-induced mutations can occur when the sequence of DNA bases is altered, disrupting the triplet code of codons

  
• Radiolysis of water


  The dissociation of water molecules into other molecular products when irradiated
• Radiolysis of water


  1. Water molecule is ionized and dissociates into an ion pair

  2. The ion pair may rejoin a stable water molecule, or the negative ion may attach to another water molecule to produce a third type of ion

  3. The unstable ions can further dissociate into H+ and OH- ions, and H* and OH* free radicals

  
• Free radical


  An uncharged molecule with a single unpaired electron, highly reactive and capable of diffusing through the cell and disrupting bonds to produce point lesions

  
• The H* and OH* free radicals, as well as hydrogen peroxide and the hydroperoxyl radical, are considered the principal damaging products of water radiolysis

  
• Free radicals can also be formed from organic molecules, and in the presence of oxygen, additional reactive free radical species can be produced

  
• Direct effect


  When the ionizing event occurs on the target molecule
• Indirect effect


  When the initial ionizing event occurs on a distant, non-critical molecule, which then transfers the energy to the target molecule
• The principal effect of radiation on humans is indirect, as the body consists of approximately 80% water and less than 1% DNA
• When oxygen is present, the indirect effects are amplified due to the additional types of free radicals that are formed