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Radiation Injury Reduction Strategies: Genetics, Scavenging, and Protection

This lecture discusses strategies for reducing radiation injury, including genetic approaches, scavenging free radicals, and cellular protection mechanisms. Topics cover the repair and regeneration of damaged DNA strands, cell survival mechanisms, antioxidants, and detoxification processes. Protective agents like SOD, Vitamins E, A, C, and minerals such as selenium are highlighted to combat radiation-induced damage. The importance of enzymatic and non-enzymatic scavenging of free radicals to prevent cellular damage is emphasized. Melatonin and its role in reducing oxidative stress and protecting against radiation injury are explored. The lecture also delves into targeting protective agents to sensitive sites in the cell for enhanced effectiveness.

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Radiation Injury Reduction Strategies: Genetics, Scavenging, and Protection

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  1. Twelfth lecture

  2. Direct DNA strands Damaged molecules Cell death Stem cell depletion Organism death Free radicals Superoxides peroxides H2O O2 Indirect Hydrogen transfer Enzymatic repair Scavenging Hypoxia Antioxidants Detoxification Repopulation Increased survival STRATEGIES FOR REDUCING RADIATION INJURY Neutrons and alpha PROTECTION REPAIR REGENERATION X and gamma rays GENETICS Reduce concentration of reactive intermediates Restore molecular function Stimulate proliferation of surviving stem cells

  3. Antioxidants Aminothiols Eicosanoids Genetic approaches SCAVENGING HYPOXIA Enzymatic Non-enzymatic PROTECTION AGAINST CELLULAR DAAMGE Cysteine analogues Arachidonic acid * Define encoding gene sequences for enzymes involved increasing SOD synthesis * PAF * DiPGE2 * GE2 * LTC4 * Ex. WR compounds * 1/2 hr before irradiation * DRF * Vit. E, A, C, * Minerals:Se * Gluitathione * Melatonin * SOD * GSH-Px * GSH-Rd * Catalase * Define sequence of sensitive sites and targeting protective agents to these sites

  4. H2O Mitochondria P450 oxidases Catalase Fe++ Fe+++ SOD OH-+ .OH H2O2 O.-2 2GSH Lipid peroxidation Glutathione peroxidase Glutathione reductase GSSG H2O ENZYMATIC SCAVENING O2

  5. Free radical chain reaction Extracellular fluid LOOH LOO. Membrane H2O TocOH TocO. Phospholipase A2 HO. O2 LOOH, H2O2 GSH Vit. Coxd GS-SG Vit. Cred GSH Cytosol Glutathione peroxidase Se Catalase SOD .O2 Superoxide H2O LOH GS-SG NON-ENZYMATIC SCAVENING LH

  6. Enzymes Potential changes resulting from the action of melatonin Glutathione reductase GSH Gamma-GCS GSH G-6-PDase NADPH Superoxide dismutase O2.- Catalase H2O2 Glutathione peroxidase H2O2 NO., ONOO- MELATONIN Nitric oxide synthase

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