Molecular Radiobiology

• The occurrence of molecular lesions is identified by effects on macromolecules and on water.
• Because 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 ultimate damage occurs to the target molecule, DNA, which controls cellular metabolism and reproduction.
• When macromolecules are irradiated in vitro, (outside the body or outside the cell), a considerable radiation dose is required to produce a measurable effect.
• Irradiation in vivo, (within the living cell), demonstrates that macromolecules are considerably more radiosensitive in their natural state.
• A solution is a liquid that contains dissolved substances. A mixture of fluids such as water and alcohol is also a solution.
• When macromolecules are irradiated in solution in vitro, three major effects occur: main-chain scission cross-linking, point lesion
• Main-chain scission is the breakage of the backbone of the long-chain macromolecule.
• Main-chain scission reduces not only the size of the macromolecule but also the viscosity of the solution.
• A viscous solution is one that is very thick and slow to flow, such as cold maple syrup. Tap water, on the other hand, has low viscosity. Measurements of viscosity determine the degree of main-chain scission
• Some macromolecules have small, spurlike side structures that extend off the main chain. Others produce these spurs as a consequence of irradiation.
• These side structures can behave as though they had a sticky substance on the end, and they attach to a neighboring macromolecule or to another segment of the same molecule. This process is called cross-linking.
• Radiation-induced molecular cross-linking increases the viscosity of a macromolecular solution.
• Radiation interaction with macromolecules also can result in disruption of single chemical bonds, producing point lesions.
• Point lesions are not detectable, but they can cause a minor modification of the molecule, which in turn can cause it to malfunction within the cell
• Point lesions can result in the stochastic radiation effects observed at the whole-body level
• Laboratory experiments have shown that all these types of radiation effects on macromolecules are reversible through intracellular repair and recover
• Modern molecular biology has developed a generalized scheme for the function of a normal human cell. The synthesis of proteins and nucleic acids is critical to the survival of the cell and to its reproduction.
• Molecular nutrients are brought to the cell and are diffused through the cell membrane, where they are broken down (catabolism) into smaller molecules with an accompanying release of energy.
• This energy is used in several ways, but one of the more important ways is in the synthesis of macromolecules from smaller molecules (anabolism).
• Proteins are manufactured by translation of the genetic code from transfer RNA
• Proteins are manufactured by translation of the genetic code from transfer RNA, which had been transferred from messenger RNA (mRNA).
• The information carried by the mRNA was in turn transcribed from DNA.
• Radiation damage to any of these macromolecules may result in cell death or late stochastic effects.
• Proteins are continuously synthesized throughout the cell cycle and occur in much more abundance than nucleic acids.
• Furthermore, multiple copies of specific protein molecules are always present in the cell. Consequently, proteins are less radiosensitive than nucleic acids.
• RNA molecules are less abundant than protein molecules
• the DNA molecule, with its unique assembly of bases, is not so abundant
• DNA is synthesized somewhat differently from proteins.
• During the G1 portion of interphase, the deoxyribose, phosphate, and base molecules accumulate in the nucleus.
• The molecular DNA is in the familiar double-helix form in this phase.
• These molecules combine to form a single large molecule then is attached to an existing single chain of DNA.
• As the cell moves into S phase, the ladder begins to open up in the middle of each rung, much like a zipper. Now the DNA consists of only a single chain, and no pairing of bases occurs.
• Parent DNA is said to be replicated into two duplicate DNA daughter molecules.
• DNA is the most important molecule in the human body because it contains the genetic information for each cell.
• Each cell has a nucleus that contains DNA complexed with other molecules in the form of chromosomes.
• Chromosomes therefore control the growth and development of the cell; these in turn determine the characteristics of the individual
• DNA is the target molecule for radiation damage. It forms chromosomes and controls cell and human growth and development.
• 4 radiation effects on DNA

  1. Normal 2.Terminal Deletion 3. Dicentric Formation
  2. 4. Ring Formation