Radiation Biology (HTI 5007) MSc Notes PDF

Radiation Biology (HTI 5007) Introduction to Radiobiology and Basic Cell Biology Dr LIN, Liang-Ting  What are the consequences after exposure? I stared into the microwave oven too long watching my lunch, and I will increase the risk of blindness. I text my...

Radiation Biology (HTI 5007) Introduction to Radiobiology and Basic Cell Biology Dr LIN, Liang-Ting  What are the consequences after exposure? I stared into the microwave oven too long watching my lunch, and I will increase the risk of blindness. I text my friends all night long and play games until midnight, so I will be irradiated by my cell phone and get sick. I ate the suspected radioactive foods imported from Fukushima, Japan, so I will be contaminated and sickened. I went physical exam and took an X-ray exposure on Chest, my DNA will break and my cells will mutant that may cause sickness. 2  What’s your view? Courtesy of HK01 and BBC news  That’s why radiobiology essential Have you ever been exposed to radiation? What do you feel immediately? - Pain? Discomfort? Being penetrated? What do you feel after a while? - Sore? Itch? DNA breakage? Become green when getting angry? - Side effects? The interaction between radiation and biology Medical Physicists work closely with radiation-associated biological effects, particularly in the aspects of Radiotherapy. Radiographers use radiation for medical imaging purposes 6  Overview of the Radiobiology Is a science describing radiation effect on living organisms: sequence of events that follows the absorption of energy from ionizing radiation efforts of organism to compensate the effects consequences to the organism/system Levels of effects: Molecules Cells Tissues Organs Systems Whole body 8 https://www.thinglink.com/scene/412817984508133378 Overview of the Radiobiology Those keywords in Radiobiology from the bench side to bedside 9  Levels of the radiation-induced events Molecule: free radicals, DNA, Proteins Cell: chromosomal aberrations, mutation, cell death, immortalization(carcinogenesis) Tissue/Organ: Cancer, necrosis, dysfunction, malfunction, pathogenesis Systemic/Whole body: complications, death 10  Game theory – it’s gambling All radiation-induced biological events are in a function of probability. Cannot predict individual event Events are non-selective and random May happen together Stochastic effects Cancer Deterministic effects Cataract 11  Where does the radiation come from? Natural Universe/Outer space Inner core of the earth/underground Radioisotope Sounds Magnetic fields Artificial Nuclear power plants Radioisotopes from cyclotron/generators Weapons Radio-frequency waves Electro-magnetic fields  When do radiation sources enter our lives? The sources of radiation – background radiation Medical needs (over 90% in artificial radiation) X-ray Radioisotopes Only 15% belong to artificial radiation Industrial application Power generation Examination Transportation Museum Custom  Medical exposures – radioisotopes Time, Decay, Distance, Shielding https://www.slideshare.net/Tunoo/rad-safety-at-hospitals-v-07-25jun2010-peternyan  What is Radiation, by definition? The energy transfer from one point to another through vacuum Ionizing radiation vs. non-ionizing radiation Ionizing radiation interacts with the medium of transmission The biological effect depends on the amount of energy deposited 16  Interaction – waves interact with matters Photoelectric effect (< 0.5 MeV) 17  Interaction – waves interact with matters Compton effect (100 keV ~ 10 MeV) 18 http://hyperphysics.phy-astr.gsu.edu/hbase/quantum/compton.html  Interaction – waves interact with matters 19 Griselda Saldana-Gonzalez et al. High Density Devices Applied to a Gamma-Camera Implementation, Advanced Image Acquisition, Processing Techniques and Applications, Dimitrios Ventzas, IntechOpen, DOI: 10.5772/33990.  Interaction – waves interact with matters Pair Production (> 1.022 MeV) 20 http://electrons.wikidot.com/pair-production-and-annihilation Interaction – the energy talks 1.022 MeV 21  Interaction – law of conservation of energy What is the common product in the 3 different interaction processes of x-ray with matters? How many are the products? Where do these effects impact in radiological sciences? 22 Griselda Saldana-Gonzalez et al. High Density Devices Applied to a Gamma-Camera Implementation, Advanced Image Acquisition, Processing Techniques and Applications, Dimitrios Ventzas, IntechOpen, DOI: 10.5772/33990.  Interaction – Why 0.511? Why 1.022? Photoelectric effect – the energy is able to release a photoelectron from its atomic binding energy, no scattering Compton scattering – the energy reaches the theoretical overall energy of an electron, recoiled electron and scattered photon occurred after collision Pair production – the energy reaches the theoretical combined energy of 2 electrons; a pair of electron and positron will occur via collision into nucleus. 23 Basic Cell Biology  What about “Biology” in Radiobiology? The basis of biology is “cell” 27 https://emsom.edu/anatomy-physiology-cell/  The discovery of DNA structure 1953 James Watson & Francis Crick published the double helix structure of DNA 1962 Nobel Prize Laureate 28 The discovery of DNA structure Rosalind Franklin (1920-1958) 29  The discovery of DNA structure 30 https://www.genscript.com/dna.html (modified)  The DNA structure – a double helix model 2 3 Purine: Adenine and Guanine Pyrimidine: Cytosine and Thymine 31 https://openoregon.pressbooks.pub/mhccmajorsbio/chapter/dna-structure/  Deoxyribonucleic Acid (DNA) Structure DNA is a chain of nucleotides linked by covalent bonds (sugar-phosphate bond) Hydrogen bonds connect two strands of DNA in the paring of A=T and C≡G. DNA twisted into double-helix The width between the two strands is about 2 nm Condensed into visible chromosome during mitosis (M phase) 32 From DNA to Chromosome 33  Normal cells vs. cancer cells The critical target in cell Deoxyribonucleic Acid (DNA) Are they reversible? The ability of keeping alive Immortalization Non-stop cell division Cell cycle Telomere elongation 34  The life of cycle in cells Quiescent (Q) stage M: mitotic phase; I: interphase Proliferative (P) stage  Cellular Checkpoints – Controlled Growth CyclinD1/Cdk4/6 (G1 progression); CyclinE/Cdk2 (G1/S transition); CyclinA/Cdk2 (S progression and S/G2 transition); CyclinB/Cdk1 (G2/M transition and M progression)  Cell cycle – checkpoints secure cell integrity Checkpoints ‐ Cell cycle progression is regulated by several proteins as being the Go/no-Go criteria. ‐ The stoppage of cell cycle is to assure the cell contents are intact to enter mitosis ‐ G1/S checkpoint ❑ Clear to initiate DNA synthesis ‐ G2/M checkpoint ❑ DNA is correctly synthesized ❑ Clear to enter mitosis ‐ Mitotic checkpoint ❑ Spindle fibers well-attached ❑ Chromosome can be separated Cell cycle – as an example in cancer G1 phase progression – molecular views R Static state/Quiescent Proliferation-activated  Cancer – cell doubling time (CDT) Time required for a group of tumor cells to double the number = around the time for one cell cycle The CDT of cancer cells are about 24 hours Somatic cells may not initiate cell cycle but stay in G0 phase eternally. E.g. skin cells or neuron cells https://study.com/academy/lesson/what-is-interphase-definition-stages-quiz.html  Cancer – Tumor Growth Fraction (TGF) There are actually very few situations in which all the cells in a population are proliferating. The population is consisted by proliferative (P) and quiescent (Q) cells. 𝑵𝑷 𝑪𝒆𝒍𝒍𝒔 𝒊𝒏 𝒄𝒆𝒍𝒍 𝒄𝒚𝒄𝒍𝒆 𝑻𝑮𝑭 = = 𝑵𝑷 + 𝑵𝑸 𝑪𝒆𝒍𝒍𝒔 𝒊𝒏 𝒄𝒆𝒍𝒍 𝒄𝒚𝒄𝒍𝒆 + 𝑮𝟎  Take home message – Biology Rough cell cycle: Proliferative phase (P) and Quiescent phase (Q). Cell cycle phases: G1, S, G2, and M. (G0 is considered a long-term G1). With in mitotic phase (M): prophase, metaphase, anaphase, and telophase. DNA structure is double helix with A-T and C-G pairing, where A-T are double and C-G are triple hydrogen bonds, respectively. Pyrimidine and purine 44  Death of cell – why cells go dying? Programmed cell death – signaling transduction Nutrient deprivation Catastrophic malfunction Irreversible damage / massive damage Aging 46 Death of cell – an end of cell life 47  Death of cell – Senescence Aging of cells Length of telomere – a setback of DNA replication Nobel Prize in Physiology and Medicine (2009) 49  Death of cell – autophagy Autophagy Auto- : means “self” -phagy: means “to eat” Self-eating mechanism in cells Nobel prize in Physiology and Medicine (2016) Yoshinori Ohsumi (大隅 良典) To clean up wastes/malfunction organelles To regain energy from material recycling 50 Courtesy of Nobel Prize Committee of Karolinska Institute  Mitotic death – unable to divide Masawang, K., M. Pedro, H. Cidade, R.M. Reis, M.P. Neves, A.G. Correa, W. Sudprasert, H. Bousbaa, and M.M. Pinto, Evaluation of 2',4'-dihydroxy-3,4,5-trimethoxychalcone as antimitotic agent that 53 induces mitotic catastrophe in MCF-7 breast cancer cells. Toxicol Lett, 2014. 229(2): p. 393-401.  Death of cell – Programmed cell death (PCD) Why is cell death essential? ‐ Tadpole’s tail ‐ The formation of fingers and toes ‐ The sloughing off of the inner lining of the uterus ‐ The formation of proper connection between neurons and target cells in brain ‐ Apoptosis 55  Apoptosis – what program? e.g. ionizing radiation 58 Cuda, C.M., R.M. Pope, and H. Perlman, The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases. Nat Rev Rheumatol, 2016. 12(9): p. 543-58.  Apoptosis – in sequence 1. Cell shrinkage 2. Organelle breakdown 3. Mitochondrial leakage 4. Chromatin condensation 5. Nuclear fragmentation 6. Membrane blebbing 60  Death of cell – Necrosis (in tissue) External factors: ‐ Mechanical trauma ‐ Damage to blood vessels ‐ Burn of extreme cold ‐ Ionizing Radiation Internal factors: ‐ Internal cell injury ‐ Toxins or pathogens e.g. snake venoms, bacterial toxin ‐ Involve activity of immune system 61 https://imgur.com/gallery/ice4w 63  Categorization – Necrosis vs. Apoptosis Higher Dose Lower Dose Passive process Active process 64 Death of cell – Summary Necrosis Apoptosis Higher damage Lower damage Damage-induced Spontaneous Cellular swelling Cellular shrinkage Membrane rupture Membrane remains intact ATP is depleted Energy consuming Cell lysates outburst Apoptotic body recycled DNA catastrophic degraded DNA fragmentation – ladder like In vivo, bystanders affected In vivo, individually affected Explode the house Deconstruction of the house Death of cell – an end of cell life 67