RADIOBIOLOGY IRRADIATION OF MACROMOLECULES IRRADIATION OF MACROMOLECULES In vitro is irradiation outside of the cell or body In vivo is irradiation within the body IRRADIATION OF MACROMOLECULES A solution is a liquid that contains dissolved substances. When macromolecules are irradiated in solution in vitro, three major effects occur: main-chain scission, crosslinking, and point lesions IRRADIATION OF MACROMOLECULES 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. Viscosity - the state of being thick, sticky, and semifluid in consistency • Measurements of viscosity determine the degree of mainchain scission. The results of irradiation of macromolecules. A, Main-chain scission. B, Cross-linking. C, Point lesions IRRADIATION OF MACROMOLECULES Cross-linking is the process of side spurs created by irradiation and attached to a neighboring macromolecule or to another segment of the same molecule. • Radiation-induced molecular cross-linking increases the viscosity of a macromolecular solution. The results of irradiation of macromolecules. A, Main-chain scission. B, Cross-linking. C, Point lesions IRRADIATION OF MACROMOLECULES Point lesion Any change that results in impairment or loss of function at the point of a single chemical bond. • can result in the stochastic radiation effects observed at the whole-body level • not detectable, but they can cause a minor modification of the molecule The results of irradiation of macromolecules. A, Main-chain scission. B, Cross-linking. C, Point lesions SUBCELLULAR RADIATION EFFECTS SUBCELLULAR RADIATION EFFECTS • Living cells consist of long protein chains, and some of these molecules can be broken by exposing the cell to radiation. • resulting in new molecules • these molecules cannot function like the original molecules, and so they need to be repaired • If the defective molecule is the DNA; it can result in the formation of a cancer cell • Some type of cells prefer to rebuild the molecules at certain intervals rather than repairing the damage • if the limited capacity for cell repair exceeded, the molecules will start to accumulate and affect the vital survival functions of the cell SUBCELLULAR RADIATION EFFECTS When the cell is irradiated: • radiation could pass through the cell without damaging the DNA • cell’s DNA could be damaged, but the DNA repairs itself • prevent the DNA from replicating correctly • cell death; apoptosis Radiation Effects on DNA DNA is the most important molecule in the human body. • • • • • it contains the genetic information for each cell Not abundant in the cell Inside the nucleus form the chromosomes most radiosensitive molecule Radiation Effects on DNA When an ionizing radiation interacts directly with DNA: • prevents cells from reproducing • damages critical cellular systems • can lead to cancer Chromosomes control the growth and development of the cell; these in turn determine the characteristics of the individual. • If radiation damage to the DNA is severe enough, visible chromosome aberrations may be detected. Radiation-damaged human chromosomes • Terminal deletion – there is missing end part • Dicentric formation – 2 centers • Ring formation – circular shape DNA is the target molecule for radiation damage. It forms chromosomes and controls cell and human growth and development Damage to DNA can also result to abnormal metabolic activity • Uncontrolled rapid proliferation of cells is the principal characteristics of radiation-induced malignant disease • If damage to DNA occurs within a germ cell, then it is possible that the response to radiation will not be observed until the following generation (cause of genetic effect) Germ cell - are the only cells in the body that have half the amount of chromosomes, undergo both mitosis and meiosis and in males produce the gamete, sperm. 3 principal observable effects that may result from irradiation of DNA • Cell death • Malignant disease • Genetic Damage