Radiation Effects on DNA and Chromosomes

1. Radiation Effects on DNA and Chromosomes

2. So, what do you understand by DNA anyway? DNA can be described as a long fiber that resembles a hair under a powerful microscope. The only difference is that they are much thinner and longer. The whole structure is made of two strands that are intertwined together. When cells get ready to divide, proteins attach themselves to the DNA and leads to the creation of a chromosome.

5. Because the human body is an aqueous solution that contains 80% water molecules, radiation interaction with water is the principal radiation interaction in the body. However, the ultimate damage occurs to the target molecule, DNA, which controls cellular metabolism and reproduction.

6. The effect of irradiation of macromolecules is quite different from that of irradiation of water. When macromolecules are irradiated in vitro, that is, outside the body or outside the cell, a considerable radiation dose is required to produce a measurable effect. Irradiation in vivo, that is, within the living cell, demonstrates that macromolecules are considerably more radiosensitive in their natural state.

7. In vitro is irradiation outside of the cell or body. In vivo is irradiation within the body.

8. IRRADIATION OF MACROMOLECULES • 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 lesions

9. Main-chain scission is the breakage of the backbone of the long-chain macromolecule. The result is the reduction of a long, single molecule into many smaller molecules, each of which may still be macromolecular. 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.

10. Cross-Linking Some macromolecules have small, spur-like 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.

11. Point Lesions 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.

12. At low radiation doses, point lesions are considered to be the cellular radiation damage that results in the late radiation effects observed at the whole-body level

13. Point lesions Main scission Cross-linking

14. Laboratory experiments have shown that all these types of radiation effects on macromolecules are reversible through intracellular repair and recovery.

15. Radiation Effects on DNA 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

16. The DNA molecule can be damaged without the production of a visible chromosome aberration. Although such damage is reversible, it can lead to cell death. If enough cells of the same type respond similarly, then a particular tissue or organ can be destroyed.

17. Damage to the DNA also can result in abnormal metabolic activity. Uncontrolled rapid proliferation of cells is the principal characteristic of radiation-induced malignant disease. If damage to the DNA occurs within a germ cell, then it is possible that the response to radiation exposure will not be observed until the following generation, or even later.

18. RADIATION RESPONSE OF DNA • Main-chain scission with only single strand break • Main-chain scission with double strand break • Main-chain scission and subsequent cross-linking • Base damage

19. Single strand break Base damage Double strand break Cross-linking

20. Single strand break • Most likely efficiently repaired, with little, if any , long term consequences to the cell.

21. Double strand break • Difficult for the cell to repair. They show reasonable corelaiton with cell killing. If repair does not take place, the DNA chains can separate, with serious consequence to the life of the cell.

22. Cross-linking • Between two regions of the same DNA strand • Between two complementary DNA strands • Between two completely different DNA molecules • Between DNA and protein • Important if not repaired

23. Base damage • The loss or a change of a base on the DNA chain results in the alteretion of the base sequence. Base sequence stores and transmits genetic information. It has nmajor consequences. Loss or change of base is considered a type of mutation.

24. The DNA molecule can be damaged without the production of a visible chromosome aberration. Although such damage is reversible, it can lead to cell death. If enough cells of the same type respond similarly, then a particular tissue or organ can be destroyed

25. When radiation interacts with chromosomes, the interaction can occur through direct or indirect effect. In either mode, these interactions result in a hit. The hit, however, is somewhat different from the hit described previously in radiation interaction with DNA. The DNA hit results in an invisible disruption of the molecular structure of the DNA. A chromosome hit, on the other hand, produces a visible derangement of the chromosome. Because the chromosomes contain DNA, this indicates that such a hit has disrupted many molecular bonds and has severed many chains of DNA

26. The study of chromosome damage from radiation exposure is called cytogenetics

27. A chromosome hit represents severe damage to the DNA.

28. The single-hit chromosome aberrations

29. The multi-hit chromosome aberrations

30. The multi-hit chromosome aberrations represent rather severe damage to the cell. At mitosis, the acentric fragments are lost or are attracted to only one of the daughter cells because they are unattached to a spindle fiber. Consequently, one or both of the daughter cells can be missing considerable genetic material.

31. Radiation-induced reciprocal translocations result in no loss of genetic material, simply a rearrangement of the genes. Consequently, all or nearly all genetic codes are available; they simply may be organized in an incorrect sequence.