Glossary of RadTech: RadBio: Ch.5

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Define LET.
The rate at which energy is deposited in tissue as a charged particle travels through matter
Define RBE
Relative Biologic Effect

The ability of radiations with different LET ranges to produce a specific biologic response

It is the comparison of a dose of test radiation to a dose of 250 KeV x-ray, both producing the same biologic response.
If the response of a cell to radiation is enhanced has its inherent sensitivity changed?

The inherent sensitivity has NOT changed.
What has changed is some external factor
What did Ancel and Vitemberger state first?
Inherent susceptibility of any cell to damage by ionizing radiation is the same, but the time of appearance of radiation-induced damage differs among different types of cells
What influences the appearance of damage in cells?
1. The biologic stress placed on the cell – the biggest being the necessity for division.

2. The conditions the cell is exposed to both pre and post radiation.
What are the main categories of external factors?
1. Physical Factors

2. Chemical Factors

3. Biologic Factors
What are the physical factors?
1. LET (linear energy transfer)

The rate at which energy is deposited in tissue as radiation(charged particle) travels through matter ( energy lost from the radiation).

2. RBE (relative biologic effect)

The comparison of biological effects between a dose of radiation and a dose of test radiation.
Same biologic effect = Dose of 250kev xray/Dose of test radiation

3. Dose Rate
How can the effects of different types of radiations (differing LETs), on cell survival curves be compared?
The RBE can be calculated by choosing the same survival level on each of the two curves (high LET versus low LET)
How does LET modify radiation effects?
Increasing LET values increase cell death.
Where on the cell survival curve are Neutrons most effective in causing cell death?
In the shoulder region the neutrons are 3 times (300%) more effective
What is the reason for the difference in RBEs in the shoulder region of the cell survival curve?
In the shoulder region cells can repair at this low x-ray dose, but lose that ability with the even lower dose of neutrons

Neutrons are more likely to cause Single Hit cell death
What happens to RBE as the dose is reduced?
(for different types of radiation)
RBE will not be constant over the whole dose range and will be larger as the dose is Reduced
What is dose rate?
Dose rate is the rate at which radiation is delivered
Which dose rates are most inefficient at producing cell damage?
All studies have shown LOW DOSE rates to be less efficient for producing damage than high dose rates
What happens to Survival as dose rate decreases?
Survival clearly increases as dose rate decreases
What happens to the shape of the cell survival curve with increasing dose rates?
The shape of the cell survival curve becomes much more shallow and the shoulder is nearly eliminated.
What do low dose rates allow the cell to do?
Low dose rates allow for repair to occur before enough damage has accumulated to cause cell death
What can be said about high LET radiations and dose rate effect?
High LET radiations do NOT show a dose rate effect
How much does dose rate affect cells whose survival curves have large shoulders?

And those with small shoulders?
Large dose rate effects

Small dose rate effects.
What are the different types of Chemical factors?
Radiosensitizers – chemicals that enhance radiation response

Radioprotectors – chemicals that diminish response
Which chemical has the most dramatic effect, and has universally been shown to enhance radiation response?
The chemical that has had the most dramatic effect and has universally been shown to enhance radiation response is OXYGEN
Tto be most effective when must oxygen be administered?
The oxygen effect was found to be most effective when administered simultaneously with radiation.
Not pre or post radiation exposure!!
What are the theories on how oxygen enhances radiation?
Oxygen may enhance the formation of free radicals

May draw existing free radicals into chain reactions producing new and highly damaging radical species.
Ehat can happen with many of the chemical changes that occur with an interaction of radiation in the absence of oxygen?
In the absence of oxygen many of the chemical changes that occur with an interaction of radiation are reversible

In the presence of oxygen the process of repair seems to be blocked, thus increasing damage.
How does Oxygen affect the cell survival curve?
1. The shoulder of the curve is made smaller.

2. The slope of the exponential portion is steeper.
Resulting in a decreased D0.
In what amount of Oxygen is the response greatest?
The response is greatest between 0 – 20mm Hg
What is OER?
Oxygen Enhancement Ratio

It is defined as the dose of radiation that produces a biologic response in the absence of Oxygen divided by the dose of radiation that produces the same biologic response in the presence of oxygen
What is the OER for mammalian cells?
The OER for mammalian cells is between 2 and 3
For which types of radiations is the oxygen effect most pronounced?
The oxygen effect is most pronounced for x-rays and gamma rays, much less for High LET radiations
Which is the most widely used category of Radio-Sensitizing chemicals?
The most widely tested are a category called nitroimidazoles.

The most well known of this group is RO-07-0582.
Also called Misonidazole
What is another category of Radio-Sensitizing chemicals?
Another group are the Halogenated Pyrimidines. These chemicals substitute for the base thymidine in DNA
Give two chemicals in the Pyrimidine group.
5-bromodeoxyuridine (5-budr).

5- iododeoxyuridine (5-iudr).
How do Pyrimidines work?
These substances are selectively incorporated into the DNA in place of thymidine, changing the molecule and rendering it more susceptible to radiation damage
How many cell cycles must they be present for before radiation effects will be enhanced?
They must be present for several cell cycles in order to be incorporated into the DNA, before radiation effects will be enhanced
To be effective when must Radiation Protectors be administered?
These compounds HAVE to be present AT THE TIME of the radiation exposure in order to exert their protective effect
Give one group of Radiation Protector chemicals.

WR-2721 formed from this sulfhydryl group, contains a chemical called cysteine
What is the Dose Reduction Factor (protection factor)?
The difference in dose required to achieve the same cell survival between cells with radio protectors and those without.

Meaning a larger dose of radiation was necessary to cause the same effect
Roughly how much extra dose is required to produce the same effect?
Almost twice the dose is necessary to produce a given effect
How do radioprotectors work?
These agents protect by either competing for the radiation produced free radicals

Or by giving up a hydrogen atom to the ionized molecule, which seems to neutralize the effects of the radiation
Which types of radiation are radioprotectors most effective against?
Are again most efficient with xrays and gamma rays and have only a negligible effect with high LET radiations
Which Biological factors affect radiosensitivity?
1. The position of the cell in the cell cycle at the time of irradiation has a great influence on cellular response

2. Intracellular Repair
Rank the cell phases from most to least sensitive to radiation.
M - most radiosensitive

G2 - more radiosensitive

G1 - less radiosensitive

S - least radiosensitive
What is Intracellular Repair?
This is the capability of cells to repair sublethal damage

That is damage repair between two doses of radiation. Cell survival increases between two doses as compared with a single equal dose
what ampunt of total dose is necessary when giving a fractionated dose?
A higher total dose is necessary to produce the same biologic response when the dose is fractionated than when it is given acutely
What can be said of cells surviving the first dose fraction?
Cells surviving the first dose fraction respond as un-irradiated cells to the second fraction
How long does the repair process take to be complete in the cell?
The repair process appears to be complete in the cell within 24hrs post irradiation

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