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47 Cards in this Set

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What is Radiobiology?
Radiobiology is the study of the biologic effects of radiation and the efforts of living things to deal with energy absorbed by them.
This includes the sequence of events, the organisms compensation and any damage produced.
What generalizations can be made concerning the interactions with radiation?
1) Interactions follow a
probability function.

2) Energy is deposited very quickly in tissue.

3) Radiation interactions in a cell are nonselective.

4) Changes in the cell are not unique.

5) Biologic changes take time (latent period)
5 generalizations

It may or may not interact.

10-17 of a second.

Deposited Randomly.

Can not be distinguished from other forms of trauma.

Minutes to Weeks to Years (depends on initial dose).

What are the ways radiation can interact?
1. Direct method.

2. Indirect method.
Two ways.
Describe the Direct Method.
Ionization occurs in a critical biological macromolecule (ie: DNA).
Direct ionization of a critical target.
Describe the Indirect Method.
Ionization is in the medium that the cells are suspended in. (ie: Water HOH).
80% of a cell is water
Which types of radiation are associated with each method?
Direct Method - This is the method of interaction with particulate radiations NOT electromagnetic radiations.

Indirect Method - is the interaction associated with x-rays and gamma rays.
What medium plays a key role in Indirect Action?
Water.
Since 80% of a cell is water there is a high probability of an interaction with water.
What causes cell damage after the Indirect interaction with water?
The products of this interaction
How do these by-products cause damage?
They must be able to accomplish two tasks.

1. Diffuse far enough to reach a target (DNA).

2. Be in a form that can cause damage.
Two ways
How much damage in tissue can be attributed to Indirect Action?
2/3rds
What is a Free Radical?
These free radicals contain a single unpaired electron in the outershell, rendering it chemically unstable.
Symbolized by a dot next to the chemical name. (ie: OH., or H.).
Why do free radicals have a high degree of reactivity?
Because they have an unpaired electron, the electrons remaining are not matched in their spin.
Spin
What is the process of radiation absorption in water called?
Hydrolysis of Water
Describe the process ofHydrolysis of Water.
1. ionization of a water molecule.
HOH HOH+ + e-

This free electron is captured by another water molecule giving two water ions.

HOH+ and HOH-

2. These two water ions are unstable in their current form and dissociate.
Each forming another ion plus a free radical.
HOH+ H+ + OH.
HOH- OH- + H.

3. The ion pair may recombine, forming water with no damage to the cell. H+ + OH- = HOH
This is the most common outcome with the ion pair.

4. Free radicals are extremely reactive. They also may recombine like the ions to form harmless water molecules.
H. + OH. = HOH
This is uncommon with free radicals.

5. More likely, is that they will join with other free radicals and form damaging molecules that are lethal to the cell.
OH. + OH. = H2O2
This is hydrogen peroxide and is lethal to the cell.
How long is the radiation absorption process?

How long is the Hydrolysis process?
1. 10-17 of a second

2. 10-5 seconds
How long is it before Carcinogenesis is seen?
1. It can take years to form after a latent period.
How long is it before Mutations may be seen?
Mutations passed to offspring can take generations to manifest themselves.
Define LET.

What are the units?
The rate at which energy is deposited as a charged particle travels through matter.

The units are kev/um (micro meter)
What is LET a function of?
Mass and charge.
Are X-rays and gamma rays high or low LET?
X-rays and gamma rays, having no mass and no charge are LOW LET radiations.
They are said to be sparsely ionizing.
What LET are protons, neutrons, alpha particles?
Particulate radiations such as protons, neutrons, alpha particles are said to be HIGH LET radiations.
Because of their mass and associated charges.
They are densely ionizing.
Define Relative Biologic Effect.
It is the comparison of a dose of test radiation to a dose of 250keV x-ray.

Both must be delivered under the same conditions and produce the same biological response.
Equal doses of different LET radiations do not produce the same biologic response
What does RBE (relative biologic effect) attempt to do?
RBE (relative biologic effect) attempts to compare differing types of radiations.
Equal doses of different LET radiations do not produce the same biologic response
Give the RBE formula.
RBE =

Dose in Gy from 250 keV X-ray
over
Dose in Gy from another
radiation

Both must be delivered under the same conditions and produce the same biological response.
Two items are being compared.
Which parts of the cell are least likely to survive damage?

Why?
The cell membrane and its DNA.

Many parts of the cell (enzymes and organelles) are duplicated throughout the cell. Damage to one or more of these may not be lethal to the cell.

However,The cell membrane and DNA however are present only in the necessary amounts.
Damage to either of these structures can become critical to the cells ability to survive.
Do X-rays interact with selective cell sites?
NO.
Radiation has:
No specificity
No selectivity
Targets represent potential areas for damage in the cell.
What is a target site?
Targets represent potential areas for damage in the cell.

A random ionization occurring in this area will have greater consequences to the cell than an ionizing event occurring in another poart of the cell.
Potential is key.
What two general points to be made about cell damage?.
1. much of the damage in the DNA can be and is repaired by the cell.

2. All types of DNA damage are not equal in terms of biologic significance.
List the categories of DNA damage.
1. Base Damage

2. Single strand break
Four of
What is Base Damage?
Either a change or loss of a base.
A-T or C-G
Of major consequence to the cell.
A type of mutation.
in the back bone of one chain of the DNA molecule.
Most likely efficiently repaired, inconsequential in terms of cell kill.
What is a Single Strand break?
in the back bone of one chain of the DNA molecule.

Most likely efficiently repaired.

Inconsequential in terms of cell kill.
What is a Double Strand break?
It occurs in both chains of DNA molecule.

If they are in proximity to each other they can have a significant impact on the cell.

Difficult to repair.

If they are not adjacent, they are considered single strand breaks, and are repaired.
What is Crosslinking?
It occurs either within the DNA molecule or from one DNA chain to another.

The DNA molecules become covalently linked.

Covalent links inside the chain are termed intra-strand crosslinks.

Covalent links between two different strands are interstrand crosslinks.
What general statements can be made about the effects on Chromosomes?
1. Can be observed under a microscope.

2. Can occur in both somatic and germ cells.

3. Can be transmitted during mitosis and meiosis.

4. Are equally as serious as DNA damage.
Four items.
How can radiation affect the chromosome?
Radiation can cause a break producing two or more chromosomal fragments.

The broken ends have the ability to rejoin to the ends of other chromosomes
producing mutations.
What other terms are use for these chromosomal changes?
Aberrations
Lesions
Anomalies
Three terms.
What does the time of irradiation in the cell cycle determine?
Whether they are chromosome or chromatid aberrations.
If irradiation occurs AFTER the S Phase what aberration is produced?

What is the possible consequence?
Chromatid aberrations are those produced in individual chromatids when irradiation occurs AFTER the s-phase or DNA synthesis.

In this case, possibly only ONE daughter cell will be effected.
If irradiation occurs BEFORE the S Phase what aberration is produced?

What is the possible consequence?
Chromosome aberrations occur when irradiation interacts BEFORE the S-phase.

The resultant break will be replicated IF the repair is not complete before s-phase begins.

In this case both daughter cells are effected.
What structural changes can take place in chromosomes?

Name them.
Like DNA there are four basic structural changes that can take place in chromosomes.

1. Restitution

2. Deletion

3. Rearrangement of the broken ends on the same chromosome /chromatid.

4. Rearrangement of broken ends without visible damage.
Four changes.
What is Restitution.?
The broken ends can rejoin with no visible damage to the cell.

95% of single strand breaks are repaired this way.
95% of single strand breaks are repaired this way.
What is Deletion?
Loss of part of the chromosome or chromatid during the next mitosis.
What does rearrangement of the broken ends on the same chromosome/chromatid produce?
This produces grossly distorted chromosomes.
What are the types of grossly distorted chromosomes?
1. Acentric fragments - have no centers.

2. Dicentric fragments - have two centers.

3. Ring fragments - have one center with their tails joined.
Three types
What are translocations and inversions?

What is their consequence?
The genetic material has been rearranged even without visual distortions.

Chromosome under the microscope appears normal.

However a mutation has happened.
Switching of genetic information on the same chromosome.
What happens when irradiation occurs during Mitosis?

Which specific phases are concerned?
The chromosomes clump together causing distortions and aberrations in the genetic material reaching the daughter cells.

From metaphase through anaphase.
What effects are seen if the changes are taking place in either somatic or germ cells?
Somatic damage will effect the individual.

Germ damage effects the population as a whole.