Molecular Radiobiology Module 4 Part #3

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1 Molecular Radiobiology Module 4 Part #3 Bushong - Chapter Rhodes

2 Interaction & damage is a matter of chance Energy deposited rapidly seconds Interactions are non-selective in tissue Interactions are not unique Damage occurs after latent period the latent time from minutes to years

3 Invivo In natural environment Invitro Outside of natural environment Radiation of macromolecules invitro molecules tolerate a lot of radiation Invivo less radiation is tolerated

4 Main Chain Scission Break of backbone Reduces Viscosity of solution Diagram A Cross-Linking Sticky protuberances attach sections of chains Increases Viscosity Diagram B Point Lesions Disrupts individual chemical bonds Cannot measure No Viscosity Change Diagram C All Repairable A. Main chain scission B. Cross-linking C. Point lesions 4

5 RNA & DNA RNA multiple copies of present in cell Singular copy of DNA present in cell DNA is the most Radiosensitive molecule

6 Chromosome aberrations Chromosomal aberrations leading to cell death Abnormal metabolic activity and cell multiplication Cancers Chromosome damage in germ cells - showing up in future generations

7 Main chain scission with one side rail severed A with both side rails severed - B with subsequent cross linking - C Rung breakage with separation of bases - D Change or loss of base

8 Point Mutation Single Strand Break Repair is possible

9 Double Strand Break Occur more often with higher LET Radiations More difficult for body to heal

10 Double Strand Break in same rung of ladder Complete chromosome breakage Cleaved or separated Cell death or impaired function

11 Covalent Cross-Links Molecules create sticky spurs following irradiation Between 2 places on same DNA strand (intrastrand crosslink) Between 2 DNA strands (interstrand cross-links) Between 2 DNA Molecules

12 Rung breakage causing a separation of bases A change in or loss of a base Codon set of 3 normal bases in the DNA

13 Human Body 80% water Molecules Most Prevalent Interaction Ionized H 2 O dissociates into 2 ions & breaks down to free radicals

14 Ionization H 2 O + HOH + + e - Can recombine into stable water molecule e - combines with other water molecule H 2 O + e - HOH - HOH + & HOH - are unstable and further break apart HOH + H + + OH * HOH - OH - + H * * = free radical or uncharged molecule that contains a single unpaired electron in the outer shell

15 OH* + OH* H 2 O 2 Hydrogen Peroxide H * + O 2 HO * 2 Hydroperoxyl Formation HO * 2 + HO * 2 H 2 O 2 + O 2 Many additional ways to make hydrogen peroxide that is toxic to the cell.

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17 Direct Ionizing event occurs on the target molecule Indirect Effect Ionization occurs on a distant noncritical molecule which transfers the energy of ionization to the target molecule (Free Radicals)

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19 Principle effect on humans is indirect from free radicals of H 2 O

20 Cellular Radiobiology Module 4 Part 3 Bushong Chapter Rhodes

21 Cell Transformation Mitotic Delay Interference with function Chromosome breakage Cell Death Instant Reproductive Interphase death Mitotic or Genetic Death Repair most common

22 Critical target in the cell with no replacements Critical target inactivated Cell Death DNA is critical Target Interactions are random

23 Cell death occurs if critical target is destroyed ( DNA) Could be damage inside cell, but if cell survives then not cell death. Hits may be direct or indirect Increased hits if oxygen is present with low LET

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25 Two Models Single Target- Single Hit Used for viruses, bacteria & simple cells Multitarget Single Hit Human cells complex systems

26 Due to random nature of x-rays Equal number of x-rays does not mean equal amount of damage

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28 Measure of sensitivity of the cell Dose where 37% of the cells survive Low D 37 means highly sensitive cell High D 37 means radioresistent cell

29 Cells have more than one critical target 2 or more hits required for cell death Threshold or safe dose

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31 Based on cell survival Bushong Formulas Page Orange boxes

32 Cell Type D 0 (Gy) Mean Lethal Dose Mouse Oocytes Mouse Skin Human Bone Marrow Human Fibroblasts Human Lymphocytes D Q (Gy) Threshold Dose

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