Rad Bio Exam 1

Acute tissue change

• Typically inflammatory

• Changes are the result of cells dying in the tissues within the radiation field

• Two possible outcomes

  • Regeneration- may be complete or partial

  • Replacement- original cell population replaced by a different population. usually fibroblasts

Chronic tissue change

Changes manifest after healing process

ex) loss of vascular supply to a tissue such as the intestine after mucosal regeneration has occurred

Factors in radiation response

• Volume of tissue irradiated

• Oxygenation at the cellular level

• Presence of some chemicals

• Dose rate

• Cellular kenetics

• Cellular kinetics

• Cell type

Hemopoietic (blood and lymph)

The parenchymal cells of the bone marrow and the circulating blood

• Red blood cells are the most resistant cell in mammals to radiation injury

Skin and oral mucosa

Erythema w/ early and late effects at 10 gray and above

Digestive system

• Early effects are mucosal depopulation

• late effects are repopulation, epithelial metaplasia (loss of cunftion), scarring, and stricture (obstruction of GI tract)

Male reproductive system

• Adult sperm are FPM cells - resistant

  • but chromosomal damage may be passed onto fetus

• Germinal cells are very sensitive

  • don’t shoot the balls

Female reproductive system

• 6.25Gy to both ovaries - expect sterility

• Can affect hormonal function

  • Decreased or lost above 25 Gy

• Follicular cells are more susceptible to harm from radiation

Cardiovascular system

Can cause thrombosis and possible hemorrhage\

• the heart is considered resistant but effects may be seen years later

Liver and Kidneys

Whole organ doses of 30 Gy are lethal

Central nervous system

Considered radioresistant in adults

Excitation

Electron of an atom is raised to a higher energy state but not ejected

Ionization

Energy imparted is great enough to cause an electron to be ejected

X-ray characteristics

• EM radiation

• No charge

• Frequency * wavelength= velocity of the wave

• Produced

  • Brenstrahlung

  • Characteristic

• Considered a photon

Alpha particles

• 2 protons and 2 neutrons

• 2+ charge

• short range cause they fat bastards

Directly ionizing

• Charged particles can directly disrupt atomic structure (nucleus or electrons)

• Cause damage

Indirectly ionizing (photons)

• Don’t directly cause damage

• Set in motion charged particles (electrons) which may cause damage

Photo-electric

• < 100 KeV

• Proportional to Z³

• Secondary emissions

  • PE ejected electron

  • Characteristic X-rays

  • Auger electrons

Compton scattering

• 25 KeV to 25 MeV

  • Most fall into this category

• Secondary emissions

  • CS photon

  • CS electron

Direct action of radiation

• Cause damage or biological effect by direct excitation or ionization

• Dominant process for high linear energy transfer (LET)

• Responsible for 1/3 of damage

Indirect action of radiation

• Radiation interacts with atoms and produces free radicals

• Free radicals can cause excitation and ionization

• Represents 2/3 of damage

Free radicals

• Radiation interacts w/ water

• High degree of chemical reactivity

• Atom with unpaired orbital electron in outer shell

Mitosis steps

1. Prophase

2. Metaphase

3. Anaphase

4. Telophase

Prophase

DNA organizes into identifiable chromosomes

Metaphase

DNA aligns with centromeres on equatorial plate

Anaphase

DNA separates and moves to opposite ends of cell

Telophase

Cell cytoplasm divides at equatorial plate

Functional Death

• Loss of a specific function

• Cells that do not proliferate (nerve, muscle, secretory)

Reproductive Death

• Cell can still be present

• Cell can still function

• Cell may be able to synthesize DNA

• Cell may have 1-2 mitoses but cannot sustain indefinitely

Mitotic Death

Death when attempting to divide

Apoptosis

Programmed cell death

Destroy cell function in non-proliferating systems

100 Gy

Loss of reproductive capacity

2Gy

Plating Efficiency PE

PE = (colonies counted/cells seeded) * 100

Surviving fraction

SF = (Colonies counted/ Cells seeded) * PE

D₁

• Based on initial slope of survival curve

• Reciprocal of initial slope

• Dose required to reduce fraction of surviving cells to 37% of previous value

D₀

• Based on the final slope resulting from multi-event killing

• Reciprocal of the final slope

• Dose required to reduce fraction of surviving cells to 37% of previous value

D_q

• Quasi-Threshold dose

• Measure of the shoulder of the curve

• Dose at which the straight portion of the survival curve extrapolated backward intercepts the Y-axis

• Threshold dose: Dose below which there is no effect

Extrapolation Number

Measure of width of shoulder

• If n > 10 (brads shoulder)

• If n is equal to 1.5-2.0 (narrow shoulder)

Linear Quadratic Model

S = e^{- (alphaD-betaD²)}

• S= surviving fraction

• alpha= component associated with non repairable component (double-strand break)

• Beta= component associated with repairable component (single-strand break)

• D= dose

Bystander effect

Death of (some) cells that are next to other cells who have been irradiated

• Up to 30% of bystander cells may be killed

Mitotic Death

Most common type of cell death

Prodromal Radiation Syndrome

> 100 Gy

• Time onset within 5-15 minutes

• Symptoms may reach max at 30 min

Cerebrovascular (CNS) Syndrome

• Dose:100 Gy

• Death: 24-48 hours

• Neurological breakdown

• Cardiovascular breakdown

• All organ systems are damaged

• Increase of fluid in brain leading to a build-up of pressure

GI Syndrome

Dose: 5 Gy-12 Gy

Death: 3-10 days

• Destruction of GI Mucosa

Bone Marrow (Hematopoietic) Syndrome

Dose: 2.5 Gy- 5 Gy

Death: Weeks to months

• Effect on blood forming organs

Bone Marrow Syndrome

Dose: 250 Gy to 500 Gy

Death: very lethal

• Mitotically active precursor cells are sterilized

• Blood count decreased

• Latent period of 1 to 3 weeks after prodromal syndrome