1. Radiation Protection & Biology Presentation 3 Chapter 31 Winter 2013
Irradiation of macromolecules
Radiolysis of water
Direct & Indirect effect
Target theory

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

3. 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

4. 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

5. 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)

6. 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

7. 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

8. 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

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

10. 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

11. 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?

12. 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

13. 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

14. 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?

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Missing Formulas from e-books:
Ionization: H2O + ionization => HOH+ + e-
Additional Ionization: H20 + e- => HOH-
Dissociation: HOH+ => H+ + OH* (free radicals)
HOH- => OH- + H* (free radicals)
Hydrogen Peroxide: OH* + OH* => H2O2
Hydroperoxyl Formation: H* + O2 => HO*2
Hydrogen Peroxide Formation: HO*2 + HO*2 => H2O O2
Organic Free Radical Formation: RH => RH* => H* + R*
Organic Free Radical Formation: R* + O2 => RO*2

23. THE END
Next Week Chapter 32
Mid Term in Two weeks on 2/6