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DNA Strand Breaks and Chromosomal Aberration II-Radiation Biology-Lecture Slides, Slides of Radiation Biology

Dr. Varun Kumar delivered this lecture at University of Lucknow for discussing following topics related to Radiation Biology: Types, Structural, Chromosomal, Aberration, Translocations, Balanced, Deletions, Duplications, Inversions, Pericentric

Typology: Slides

2011/2012

Uploaded on 07/03/2012

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Download DNA Strand Breaks and Chromosomal Aberration II-Radiation Biology-Lecture Slides and more Slides Radiation Biology in PDF only on Docsity! Radiation induced anaphase bridge type chromosomal aberrations in Radiation induced translocation & deletion type chromosomal aberrations broken pieces are exchanged between the two chromosomes, and the “sticky” ends rejoin. This aberration is not necessarily lethal to the cell There are examples in which an exchange aberration of this type leads 10 the activation of an oncogene. See Chapter 10 on radiation carcinogenesis, B: Diagram af a deletion. Radiation produces two breaks in the same arm of the same chromosome. What actually happens is illustrated more clearly in Figure 2.10. FIGURE 2.9 @ A; Formation of a symmetric translacation, Radiation produces breaks in two different prereplication chromosomes. The —- Effects of radiations at molecular level The various macromolecules in the cellular structures are: « Carbohydrates - Proteins « Lipids (fatty acids) Effects of radiations on carbohydrates A carbohydrate is an organic compound consists only of carbon, hydrogen, and oxygen, The carbohydrates (saccharides) are divided into four chemical groupings: monosaccharides, disaccharides, oligosaccharides, and polysaccharides For example, blood sugar is the monosaccharide glucose Primary direct action of radiation on ; carbohydrate is chain breakage, degradation, decreased viscosity. H—C—_O Maile sugars in at aa in the absence of oxygen, results in polymer ease This may be attributed to cross- CH oC inking Effects of radiations on proteins s Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. ms Aminoacids join togather to form a protein by successive coupling on amino and carboxylic groups with the elimination of water molecule. = The eligi! of energy by IR leads to structural changes in the form o - Hydrogen bond breakage ¢ Molecular degradation ¢ Intramolecular or intermolecular cross-linking Effects of radiations on cell membrane ¢ Radiation induced changes in the electrical activity of nerve indicates an increase in passive ion permeability of thye nerve axon. ¢ Similarly following 30 Gy dose, microvilli in the epithelial cells of mammalian intestine swells and eventually burst & bloted Effects of radiations on lysosomes - According “enzyme release hypothesis”, following radiation induced membrane damage, the unplanned release of enzyme occurs inside the cell and causes its death. « Such increased permeability of lysosomal membrane and 5-6 fold increase in lysosomal enzyme activity can be detected in spleen and thymus cells within 1-3 hours of 8.5 Gy of ©°Co, (ere laal ante oN AS - The free lysosomal enzymes are capable of damaging proteins, polysaccharides and lipids Effects of radiations on ER - ER is a system of membranes that run throughout the cytoplasm and to which many enzyme systems are attached, These enzymes require an intact membrane for full activity. « When membrane of ER is damaged by radiation, enzyme activity is impaired. Secondly, ribosomes are attached to the ER system and it is on ribosomes that the mRNA code is translated., into the a acid sequence, giving a specific protein molecule. Radiation damage to the ER may reduce the protein synthesis Radiation effect on DNA synthesis & division delay « G, Blockage seems to be due to interference with the chromatine condensation process that is essential for the formation of mitotic chromosomes and this occurs when DNA is in close association with the nuclear envelope - It is difficult to summarize the post —irradiation depression in DNA Synthesis because it is not dose dependent But also depend on the phase of the cycle at which radiation is given. For example, In one cell line 5 Gy given to cells in mitosis caused 70% reduction in DNA synthesis while same dose (5Gy) given to G, cells produced only 20 deficiency in DNA Radiation effect on DNA synthesis & division delay « It means that mitosis & G,/S border are the most sensitive phases ¢ It is concluded that division delay leads to delay in DNA synthesis and overall reduction in the amount od DNA synthesis. Deficient DNA synthesis leads to RNA synthesis and so deficient of essential proteins Nuclear damage Vs Cytoplasmic in following IR Q: Is it possible to kill cell, if only cytoplasm or only nucleus is irradiated? A: As majority of informations reside in the nucleus as genetic code in DNA so it is expected that any damage to nucleus will be of primary importance whereas damage to cytoplasm will be of secondary importance. T support the answer some experiments can be perormed.
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