Chapter 3 - Radiosensitivity And Cell Interaction

Front 1

What cells are considered radiosensitive?

Back 1

Lymphocytes
Spermatogonia
Erythroblasts
Intestinal Crypt Cells

Front 2

What cells are considered to have moderate sensitivity?

Back 2

Endothelial
Osteoblasts - bone forming
Spermatids
Fibroblasts - Connective tissue

Front 3

What cells are considered to have low sensitivity?

Back 3

Muscle
Nerve
Chondrocytes - cartilage

Front 4

What is the most sensitive phase of cell production?

Back 4

Early interphase - late G1 and early S phase

Front 5

When are cells most radioresistant?

Back 5

Late S phase

Front 6

What are the three possible scenarios of cell irradiation?

Back 6

-Slow down of cell mitosis (low doses of radiation)
- Interphase death (cell death before mitosis - highly mitotic cell dies)
- Cell death ( large doses to sensitive cell type)

Front 7

Factors of biological damage

Back 7

- Radiation interacts with cells by chance
- First deposit is given rapidly
- Interaction within cells is random
- Hard to determine if damage is from radiation
- Changes can take some time, are dose dependent, and vary from minutes to years

Front 8

What is LET?

Back 8

Linear Energy Transfer - The average energy deposited per unit path of length.
- Low LET x-ray and gamma radiaiton, short wavelength and high energy, without mass or charge.
- Causes sub-lethal damage to DNA which can be repaired.
-Lower LET = less ionization
- Enough energy to pass through patient. Smaller amount of radiation exposure.
- Low QF

Front 9

High LET radiation

Back 9

Particles that have great mass and charge
-Alpha particles - 20 QF
- Low penetration and travel little distance in tissue
- Loses energy in tissue causing ionization.
- As LET increases, so does the biological effect.

Front 10

What is RBE?

Back 10

Relative Biological Effect
- Dose of test radiation to dose of 250 keV necessary to produce given effect.
- RBE ranges from less than 1 to greater than 20.

Front 11

What factors effect RBE?

Back 11

Radiation type
cell or tissue type
physiological condition
dose rate

Front 12

What is the relationship between RBE and LET?

Back 12

As LET increases, RBE increases
Low LET radiation have low RBE
High LET radiation have high RBE
- Low LET (xray) = low biological effect

Front 13

What is the oxygen enhancement ratio?

Back 13

Ratio of radiation dose required to cause a particular response to cells or organism in an oxygen deprived environment to the radiation required to cause an identical response under normal oxygen conditions.

Front 14

What are some other factors influencing radiosensitivity?

Back 14

Age
- Most radiosensitive after birth
- Radiosensitivity declines as we continue to age
- As we reach old age we become more radiosensitive
Gender
- Females can tolerate 5-10% more radiation than males

Front 15

On what three levels does radiation effect biological damage?

Back 15

Cellular
Organic
Molecular
-Damage always begins on molecular level
-Changes molecules that effect normal cell function
- Somatic cell exposure - body processes
- Germ cell exposure - future generations affected

Front 16

What is effected in direct action?

Back 16

DNA
RNA
Proteins
Enzymes
(doesn't occur in xray)

Front 17

What is direct effect of radiation?

Back 17

Radiation interacts with the cell at the DNA level or with a macromolecule

Front 18

What is indirect effect of radiation?

Back 18

Radiation interacts in the cell suspension, water - this is thought to occur most often - Radiolysis

Front 19

When is direct interaction most likely?

Back 19

With high LET radiation
- Direct interaction with key macromolecules causing a breakage in the molecules chemical bonds
- It is a direct ionization of a critical molecular target, such as DNA, RNA, Protein, Enzymes

Front 20

When does indirect interaction occur?

Back 20

When the interaction is with the water molecules of the cell, causing damage to key macromolecules indirectly.

Front 21

Describe radiolysis

Back 21

1. Water molecule is irradiated, it absorbs energy and dissociates into a positive water ion (H2O+) and an electron (e-).
This is represented by - Radiation + H2O > H2O+ + e-
2. The free electron will combine with another water molecule to produce a negative water ion (H2O-)
Represented by - e- + H2O > H2O-
3. Since the two ions are chemically unstable, H2O+ (H2O-), each will dissociate to produce a hydrogen ion (H+), a hydroxyl ion (OH-), hydrogen free radical (H*), and a hydroxyl free radical (OH*).
Represented as - H2O+ > H+ + OH* and H2O- > H* + OH-
4. The final products of the dissociation of water by radiation are two ions (H+, OH-) and two free radicals (H*, OH*).
5. While the two ions will recombine to form water, the free radicals can also combine to form water with no cell damage. H+ + OH- > H2O and H* + OH* > H2O
6. They can also combine with other free radicals to form cytotoxic molecules such as hydrogen peroxide and hydroproxyl radicals.
Hydrogen Peroxide - H2O2 : OH* + OH* > H2O2 - Immediate cell death
Hydroproxyl radical - HO2* : H* + O2 > HO2* - can dissassociate and cause more problems.

Front 22

What is main chain scission?

Back 22

When the thread of backbone of the long chain molecule is broken. (Radiation cutting DNA strands)

Front 23

What is cross linking?

Back 23

Spur extensions of macromolecules after irradiation, develop sticky ends, causing macromolecules to connect with another macromolecule.
- Molecules reconnecting to other DNA - Thicker strand. Unlikely to survive- could cause abnormality.

Front 24

What are point lesions?

Back 24

result in a disturbance of single chemical bonds - creates molecular lesions.
- May cause molecular changes, which cause incorrect cell function.
- Strands don't reconnect
- Low radiation - xray
- More likely than cross linking or chain scission.

Front 25

How radiosensitive is DNA?

Back 25

Very radiosensitive
- Can cause Chromosome abberations and disturb metabolic activity

Front 26

How radiosensitive is RNA?

Back 26

Moderate sensitivity

Front 27

What is single hit chromosome aberration dependent on?

Back 27

Stage of reproduction
-G1 phase - Damage is passed on during replication
- S phase - Chromatid deletion - Genetic information is passed on damage
- G2 - Damage is replicated and passed to daughter cell

Front 28

What occurs in Multi-hit chromosome aberration?

Back 28

Two hits to one chromosome

Front 29

What occurs in multi-hit aberration during G1?

Back 29

Ring chromosome is produced
- If neighboring chromosomes each suffer one hit and recombine it produces a dicentric (chromosome with two centers or centromeres)
- Can result in cell missing significant genetic information

Front 30

What is reciprocal translocation?

Back 30

Multi-hit chromosome aberration
- genes become rearranged
- Genetic material is sequences incorrectly
- Two chromosomes are split, then ends are switched and reattached to other chromosome.

Front 31

What is Dose Response Relationship, and what are the types?

Back 31

Graphic representation of effects of radiation in relation so dose received.
Linear - An observed response is directly proportional to dose.
Non-linear - Observed response is not directly proportional to dose.
Threshold - There is a radiation level below which the affect will not occur
Non-Threshold - and radiation exposure will cause the affect.

Front 32

What is Target theory?

Back 32

If master molecule is hit by radiation, the cell could die or cease function.
- DNA is the irreplaceable master molecule or target molecule.
- Other molecules can be hit and destroyed by radiation with little effect on the cell.