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

Irradiation of Macromolecules 3 major effects when macromolecules are irradiated in vitro: A. Main-chain scission 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

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 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)

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

Radiosensitivity in Proteins 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 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 RNA DNA MORE

DNA in the Cell Cycle G1 DNA is in the double helix form S Ladder opens up @ middle of each rung Also called the zipper phase G2 Twice as much DNA as in G1 Why?

Comments There are twice as many DNA in G2 as the S or zipper phase has just been completed In the S or zipper phase the DNA replicates or splits in half

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?

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

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

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?

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

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

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

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, non-critical molecule & the energy is transferred to the DNA it is an indirect effect It is not possible to distinguish between a direct & indirect effect

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

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

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