Radiation Protection Biology Presentation 3 Irradiation of macromolecules

Radiation Protection & Biology Presentation 3 • Irradiation of macromolecules Chapter 31 • Radiolysis of water • Direct & Indirect effect • Target theory Medical Radiography Program

Irradiation of Macromolecules » 3 major effects when macromolecules are irradiated in vitro: A. Main-chain scission Medical Radiography Program B. Cross-linking C. Point lesions

Main-chain Scission » The breakage of the thread or backbone of the long-chain macromolecule » The long single molecule is reduced into smaller molecules (still a macromolecule) » Main-chain scission does two things: ◦ reduces the size of the macromolecule ◦ reduces the viscosity of the solution Medical Radiography Program

Main-Chain Scission » A viscous solution is very thick and slow to flow. Viscosity measurements determine the degree of main chain scission. ~ cold maple syrup has a high viscosity ~ tap water has low viscosity ~ HIGH Medical Radiography Program LOW

Crosslinking » Some macromolecules have small spur like molecules extending off the main chain » Some of these spurs are like sticky flypaper & grab a nearby macromolecule or another part of the same molecule » Crosslinking increases the viscosity of a macromolecular solution (adds strength to solution) Medical Radiography Program

Point Lesions » Disruption of single chemical bonds that result in point lesions » Point lesions can cause modification of the molecule which can cause it to malfunction in the cell. » Point lesions are the cellular radiation damage that results in late radiation effects at the body level Medical Radiography Program

Radiosensitivity in Proteins are less radiosensitive than Nucleic Acids (NA) because: ◦ proteins are continuously synthesized throughout the cell cycle ◦ There are more of them than NA ◦ multiple copies of specific protein molecules are always present in the cell ◦ LESS Proteins Medical Radiography Program Nucleic Acids MORE

Radiosensitivity of RNA & DNA » RNA radiosensitivity is in between DNA and protein ~ Multiple copies of both types of RNA are present in the cell » DNA is the most radiosensitive macromolecule ~ Contains the genetic information for the cell ~ Controls cell & human growth & development ~ There are not multiple copies LESS Proteins Medical Radiography Program RNA DNA MORE

DNA in the Cell Cycle » G 1 ~ DNA is in the double helix form » S ~ Ladder opens up @ middle of each rung ~ Also called the zipper phase » G 2 ~ Twice as much DNA as in G 1 ~ Why? Medical Radiography Program

Comments » There are twice as many DNA in G 2 as the S or zipper phase has just been completed » In the S or zipper phase the DNA replicates or splits in half Medical Radiography Program

DNA Radiation Damage » If severe, visible chromosome aberrations may be seen ~ damage to DNA can lead to abnormal metabolic activity • rapid proliferation of cells main characteristic of radiation-induced malignant disease » If the damage is to a germ cell, the response may not be seen until the next generation. ~ Why? Medical Radiography Program

Comments » Radiation damage to a germ cell probably won’t damage the person (unless it causes sterility) » The damage will be seen when the damage is passed down to the child or grandchild Medical Radiography Program

Types of Damage to the DNA A. Main-chain scission: only one side rail cut B. Main-chain scission: both side rails cut C. Main-chain scission and cross-linking D. Rung breakage causing the bases to separate E. A change in or loss of a base Which can be repaired? ◦ The first four, ◦ a change in or loss of a base CANNOT be repaired Medical Radiography Program

Three Main Observable Effects of Radiation Damage to DNA » Cell Death » Malignant Disease » Genetic Damage » Which of the above are Somatic Damage and which are Genetic Damage? Medical Radiography Program

Comments » Cell death and malignant disease are to the person who was irradiated therefore they are somatic damage » Genetic damage is the damage that is inherited by the child, grandchild, great grandchild, etc. » Even damage to the germ cell is somatic as it is to a cell in the body of the person who was irradiated Medical Radiography Program

Radiolysis of Water » Human body is ~80% water » What happens when water is irradiated? ◦ Ions are formed Ion = electrically charged particle ◦ Free radicals are formed free radical = a chemical molecule that has an unpaired electron Medical Radiography Program

Radiolysis of Water » Free Radicals ~ highly unstable ~ tries to steal electrons, which oxidizes the other molecule ~ free radicals are oxidizing agents • FR contain excess energy that can be transferred to other molecules disrupting bonds and producing point lesions far from initial ionization Medical Radiography Program

Direct and Indirect Effect » Radiation “hits” are random » If the initial ionizing event hits the DNA it is called a direct effect » If the initial ionizing event is on a distant, noncritical molecule & the energy is transferred to the DNA it is an indirect effect » It is not possible to distinguish between a direct & indirect effect Medical Radiography Program

Comments » FOR EXAMPLE: If someone threw a grenade into a classroom filled with 20 people… » One person is directly hit (and killed) by the grenade. This is a direct hit » 10 people are killed by the blast of the grenade by not directly hit » This is an indirect hit Medical Radiography Program

Definitions » Cell cycle time/Generation time ~ The average time from one mitosis to another » Age-response function ~ The cell’s change in radiosensitivity depending upon the phase in the cell cycle » Hypoxic - low oxygen » Anoxic - no oxygen Medical Radiography Program

Definitions- some review » Catabolism ◦ Macromolecules broken into smaller sections » Anabolism ◦ Macromolecules made from smaller molecules » Proliferate ◦ reproduction or multiplication of cells » In vitro - outside of the body » In vivo - inside of the body Medical Radiography Program