Mosby's ARRT RT Board Review: RADIATION BIOLOGY

Specific tissue responses are influenced by multiple factors such as:

1. Total dose

2. Radiation type

3. Cellular sensitivity to radiation

4. Volume of tissue irradiated

5. Protraction (period of time over which total dose is absorbed)

6. Fractionation (fraction of total dose given per unit of time)

What is a major molecule in the body?

Water (H2O), makes up 80% of the body

What leads to manifested responses in living tissue to radiation?

Encounters between water molecules and radiation

What happens when water is irradiated?

The chemical bond between hydrogen and oxygen atoms breaks, producing free radicals.

What is a free radical?

An uncharged molecule that contains a single unpaired electron in its outer shell.

What are the products of the irradiation of water?

An ion pair H+ and OH− and two free radicals H+ and OH

What is the lifespan of free radicals?

They have a short life span but can interact with neighboring cells.

Which free radicals cause the majority of radiation damage?

OH (hydroxyl free radical) and hydrogen peroxide (H2O2)

Other than water, what molecules can demonstrate the effects of radiation exposure?

Proteins, lipids, carbohydrates, and nucleic acids.

What are the largest organic molecules?

Nucleic acids: DNA and RNA.

What is the role of DNA and RNA in cells?

They are responsible for cellular structure and function; they provide the map for developing cells.

What is one guaranteed means for cell death?

To interrupt transcription and prevent the synthesis of DNA in the parent cell.

What is the primary target for the greatest damage to the cell from radiation?

DNA.

Direct effect!

Why is DNA difficult to target during radiation therapy?

Because it is a small molecule located in the small cell nucleus.

What can the effect on DNA following irradiation lead to?

A variety of consequences involving the nitrogenous bases or chromosomes.

What can excitation or ionization events lead to in tissues?

A small increase in temperature at the site or breaking of chemical bonds.

What type of energy is used for imaging and radiation therapy?

Ionizing radiation. (indirect effect)

Are ionizing events more likely a consequence of direct or indirect effects?

Most likely they are a consequence of indirect effects.

What is sublethal damage in the context of DNA?

Sublethal damage refers to DNA damage that can be repaired, allowing cells to recover and resume normal function.

What can be a permanent consequence of DNA damage?

Permanent DNA damage may ultimately lead to cell death.

What do favorable effects of radiation therapy depend on?

Favorable effects of radiation therapy depend mostly on random encounters with other parts of the cell, not the nucleus.

What can radiation interactions damage besides DNA?

Radiation interactions may lead to damage of the cell membrane and/or organelles in the cytoplasm.

What is the term for cell division in germ cells?

Meiosis

What is the term for cell division in other types of cells?

Mitosis

What are the four phases of division in nongerm cells?

Mitosis, Gap 1, DNA synthesis, and Gap 2

What does Gap 0 indicate in the cell cycle?

A period of rest

Which phase of the cell cycle is most sensitive to radiation?

M phase

Which phase of the cell cycle is most resistant to radiation?

S phase

What is the term for the proportion of cells in mitosis?

Mitotic index

Why is knowledge of cellular division patterns important in chemotherapy?

It influences treatment regimens such as bolus injection or continuous infusion.

What is the typical generation time for cell populations?

8 to 30 hours

What are the potential effects of radiation on cells?

Radiation may cause interphase death, delay in division, or reproductive failure.

What happens to the mitotic index as radiation dose increases?

The mitotic index declines, and the rate of decline becomes faster with increased radiation dose.

What does the decline in the mitotic index eventually lead to?

It leads to cessation of increased cell number.

How does radiation affect the delay in reentering the mitotic phase?

The delay increases as radiation doses accumulate.

What can prolonged division delay due to radiation lead to?

Prolonged division delay will eventually lead to cell death.

What does the cell survival curve describe?

The relationship between the radiation dose and the proportion of cells surviving.

How should the cell survival curve be plotted?

On logarithmic graphs, with the dose along the x-axis and surviving fraction on the y-axis.

What are some variables that may affect the cell survival curve?

1. Radiation type 2. Cell type 3. Cell vasculature and oxygenation 4. Phase of cellular division at time of exposure.

What are the two models used to plot cell survival?

Single-hit, single-target theory and single-hit, multiple-target theory.

Which model is used to plot the survival of primitive cells such as bacteria and viruses?

Single-hit, single-target model.

What characterizes the survival curve of primitive cells in the single-hit, single-target model?

There is likely no shoulder region and one hit would likely hit a critical part of the cell.

How are mammalian cells plotted in terms of cell survival?

On a single-hit, multiple-target curve.

What are some critical portions of mammalian cells that can be targeted?

DNA, chromosomes, cytoplasm and its contents, water molecules, proteins, and gate-keeping membranes.

Is radiation therapy usually administered using single doses?

No, it is not usually administered using single doses.

What can be extrapolated from the consequence of exposed cells having multiple targets to a single dose?

It can be applied to standard fractionation.

What happens when standard fractionated radiation is administered?

Target hits are random; if hits are uniform, a more rapid cell death could be observed.

What does Dq stand for in radiation biology?

Dq = quasi-threshold dose; dose required to initiate a steady decline in the mitotic index; dose causing sublethal damage.

What is D37 in radiation biology?

D37 = the dose required to leave 37% of cells surviving in the straight-line portion of the curve; relates to single-hit, single-target theory.

What does Do represent in radiation biology?

Do = the dose range for death of 63% of cells in the straight line portion; most reliable value for determining cell sensitivity; relates to multiple-target, single-hit theory.

What is the meaning of N in radiation biology?

N = extrapolation number; relative target number in the cells irradiated and a measure of the shoulder.

What happens to the surviving fraction of rapidly dividing and well-oxygenated cells exposed to high LET radiation during the M phase as the dose accumulates?

The surviving fraction of cells rapidly decreases.

What does LET describe?

The average energy deposited per unit of path length to a medium by ionizing radiation.

Why do particulate radiations have a high LET?

Because of their charge and heavy mass, which allows energy to be deposited more densely.

What is the effect of high LET radiation on normal and cancerous tissue?

The biologic effect is greater due to denser energy deposition.

What does Relative Biologic Effectiveness (RBE) compare?

The effectiveness of a test radiation to the dose of 250 KV x-ray.

What does RBE relate to in terms of radiation?

The ability of radiation with different LETs to produce the same biologic effect under the same conditions.

Do equal doses of different LET radiations produce the same biologic effect?

No, they do not produce the same biologic effect.

What does the oxygen enhancement ratio (OER) compare?

It compares the doses required to reduce survival to a certain level in hypoxic and oxygenated conditions.

OER = Dose (hypoxic) / Dose (oxic)

Anoxic (lack of oxygen) / Aerobic (require oxygen to survive)

What is true about hypoxic cells in terms of radiation?

Hypoxic cells are radioresistant.

(aerobic cells= require oxygen to survive and function)

Why is it critical to detect and treat tumors soon after diagnosis?

As tumors grow, a substantial portion becomes hypoxic.

How do well-oxygenated tumors respond to radiation compared to poorly oxygenated tumors?

Well-oxygenated tumors respond to radiation more readily than poorly oxygenated tumors.

When is the response of oxygenated cells to radiation exposure most pronounced?

It is most pronounced when sparsely ionizing radiation, such as x-ray, gamma, and electrons, are applied.

What are changes seen within days or weeks of radiation exposure called?

Deterministic or nonstochastic effects

What are changes seen after months or years of radiation exposure called?

Stochastic effects

In what situations may immediate effects of radiation be observed?

In nuclear accidents with extremely high total doses and exposure rates

What are some responses of tissues following significant doses of radiation?

Vascular dilation, cellular inflammation, and tissue necrosis at high doses

What are the four progressive stages of tissue response observed in irradiated skin?

They are easily observed when the absorbed dose exceeds 50 Gy:

1. Epilation

2. Erythema

3. Dry desquamation

4. Wet desquamation

What does TD 5/5 represent in radiotherapy?

The dose that would likely cause 5% of an exposed population to realize an adverse late effect in 5 years following exposure.

What factors are considered when documenting tolerance doses (TD) for normal mammalian tissues?

The sensitivity of tissue exposed, the volume of tissue exposed, and widely used fractionation schedules.

What does TD 50/5 represent?

The dose that would likely cause 50% of an exposed population to realize an adverse late effect in 5 years following exposure.

What happens when there is a deviation from the standard fractionation scheme?

It results in a different biologic response in both normal and cancerous tissue.

What is the modern formula used when standard fractionation is interrupted or varied?

The biologic effective dose (BED) formula.

What is the formula for biologic effective dose (BED)?

BED = (nd) relative effectiveness.

In the BED formula, what does 'nd' represent?

Total dose.

What is the relative effectiveness in the BED formula?

Relative effectiveness = 1 + d/α.

What is the reference dose for early effects (α) accepted as?

10 Gy.

What should be substituted for α when considering late effects in the BED formula?

β, which is the reference dose of 3 Gy.

What do isoeffect lines show?

The relationship between total dose and overall treatment time for a specific tissue response.

What types of tissue responses can isoeffect lines represent?

Early skin reactions, acute effects, late tissue responses such as necrosis, or the development of secondary cancers.

What type of dose response curve shows deterministic or early effects?

No threshold & linear

Variables: Dose & Severity of effect

What do dose response curves showing stochastic effects typically have?

Threshold & linear/nonlinear (depending on the endpoint)

Variables: Dose and Probability of the late effect

In which individuals may stochastic effects be seen?

In the individual exposed or in the offspring

What type of populations have whole body effects been studied in?

Small populations of people such as victims of nuclear accidents.

What are the three phases of response to whole body radiation?

Prodromal, manifest syndromes, and latent.

What is the LD 50/30 or LD 50/60 dose that could lead to death within 30 to 60 days without medical intervention?

A one-time dose of 300 to 500 cGy.

What factors influence the likelihood of progressing through the phases of radiation response?

Total dose and dose rate.

What are some prodromal symptoms of radiation exposure?

Nausea, vomiting, fatigue, fever, hypotension, and diarrhea.

What are the types of manifest syndromes associated with radiation exposure?

Hematopoietic, gastrointestinal, and cerebrovascular.

What early effects can radiation have on an unborn embryo or fetus?

Spontaneous abortion or death in utero.

As low as .05 Gy

How does the lethal dose of radiation to the unborn change during the second and third trimesters?

Lethal radiation doses increase as cells mature.

What potential damage can occur to a newborn following radiation exposure?

Damage to the central nervous system and/or permanent damage to undeveloped germ cells.

What are some late somatic effects of radiation exposure?

Radiation induced cancers, cataract formation, chronic bone marrow depression, shortened life span, and mutations in germ cells.

What are latent genetic effects of whole body radiation exposure?

They may be seen in the offspring of whole body exposure victims.

What must be considered when using whole body radiation therapeutically?

Both somatic and genetic, early and late effects of whole body radiation response.

What factors are considered when establishing annual dose limits for radiation workers and the general public?

Both somatic and genetic, early and late effects of whole body radiation response.

4 Rs of Radiobiology.

Used to justify fractionation.

. Repair

. Reoxygenation

. Repopulation

. Redistribution (reassortment)

What is the dose range for Hematopoietic syndrome?

300-800 cGy

What is the time until death without rescue for Hematopoietic syndrome?

10-15 days

What is the dose range for Gastrointestinal syndrome?

1000-5000 cGy