Chapter 7 Notes (Molecular and Cellular Biology)

Radiation Biolgy

Branch of biology concerned with effects of ionizing radiation on living systems

electrons

Ionizing radiation damages living systems by removing ______________ from atoms

Bond

Once an atom is ionized, it will not ______________ properly in molecules, which can ultimately affect the normal function of the organism

Linear Energy Transfer (LET)

Average energy deposited per unit length of the radiation’s path (track) through tissue

Increases

When LET increases, the likelihood of producing a biologic response ______________

Low LET Radiation

X-rays and gamma rays result in this type of radiation; short wavelength and high frequency; mainly causes damages through indirect action that involves production of free radicals (from radiolysis of water)

Free radicals

Formed from the indirect action of radiation causing the radiolysis of water; are very unstable and extremely reactive

X-rays and Gamma rays

These are two types of radiation that result in LOW LET radiation

Short and high

Low LET radiation causes ______________ wavelength and ______________ frequency

Indirect action

When Low LET interacts with tissue it causes damage mainly from ______________.

High LET radiation

Radiation caused by alpha, ions of heavy nuclei; charged particles released from interactions between neutrons and atoms, low-energy neutrons; long wavelength and low frequency; exhaust their energy in a shorter length of track and cannot travel or penetrate as far so they are more destructive to human tissue

High; exhaust energy in a shorter length of track and cannot travel or penetrate as far

Which LET type is more destructive: high or low? Why?

Alpha, ions of heavy nuclei, charged particles released from interactions between neutrons and atoms, low-energy neutrons

What type of radiation will result in High LET radiation?

Long; low

High LET radiation consists of ______________ wavelength and ______________ frequency particles.

DNA

The higher the LET the more likely to cause damage to ______________

Internal contamination; multiple-strand breaks; repair enzymes

High LET radiation is of greatest concern when ______________ is possible = when a radionuclide has been implanted, ingested, injected, or inhaled; potential exists for irreparable damage because ______________ in DNA are possible; if damage is too severe, ______________ are not effective at undoing damage and cell death is likely

Relative Biologic Effectiveness

relative capabilities of radiation with differing LETs to produce a particular biologic reaction

Increases

Biologic damage produced by radiation escalates as the LET ______________

Directly

LET and RBE are ______________ proportional but identical doses of radiation of various LETs do NOT render the same biologic effect

X-rays, beta particles, gamma rays

These types of radiation all carry a quality factor of 1

Alpha particles, fast neutrons

These types of radiation all carry a quality factor of 20

Radiation Weighting Factor (W_R)

Quality factor is similar to ______________, which is used to calculate equivalent dose (EqD) to determine ability of a dose of any kind of ionizing radiation to cause biologic damage

Oxygen Enhancement Ratio

When irradiated in an oxygenated or aerobic states, biologic tissue is more sensitive to radiation than when it is exposed to radiation under anoxic or hypoxic conditions

radiation dose required to cause biologic response WITHOUT oxygen divided by radiation dose required to cause biologic response WITH oxygen

3.0; 1.0

X-rays and gamma rays (low LET), have an OER of about ______________ when radiation dose is high; OER of high LET radiation is approximately equal to ______________

Law of Bergonie & Tribondeau

Young cells are more vulnerable = stem, immature, precursor, undifferentiated are all radiosensitive

Molecular, Cellular, Organic

In living systems, biologic damage resulting from exposure to ionizing radiation may be seen on what 3 levels?

Somatic

If a sufficient quantity of ______________ cells are affected, the entire body process may be disrupted

Germ/Genetic

If radiation damages the ______________ cells, the damage may be passed on to future generations

Direct

biologic damage occurs as a result of ionization of atoms on master, or key, molecules (like DNA) to become inactive or fundamentally altered

Indirect

effects produced by reactive free radicals that are created by interaction of radiation with water (radiolysis of water)

5

Direct action occurs ______________ percent of the time; ionization results in breakage of chemical bonds causing them to become abnormal structures, which leads to inappropriate chemical reactions

95

Indirect action occurs ______________ percent of the time after the production of free radicals and ions

80

What percentage of the body is water?

1 millisecond; no; chemical bond

Free radicals exists for about ______________; they have ______________ electrical charge; they’re highly reactive as they will pair with another electron to break a ______________; they can travel through the cell to destructively interact with other molecules located at a distance from their place of origin

Hydrogen (H*) and Hydroxyl (OH*)

The presence of these 2 radicals are critical because they can produce undesirable chemical reactions and cause biologic damage by transferring their excess energy to other molecules to either break chemical bonds or cause point lesions

2/3

Approximately what portion of all radiation induced damage is caused by the hydroxyl radical?

Hydrogen Peroxide (H₂O₂)

Two Hydroxyl radicals (OH*) can bond to form ______________ which is toxic to the cell

Hydroperoxyl radical (HO₂)

This radical is formed when a free hydrogen radical combines with molecular oxygen (O₂)

Hydrogen Peroxide and Hydroperoxyl radical

What are the 2 primary substances produce biologic damage directly after the radiolysis of water

Single-Stranded Break

radiation interacts with DNA, energy transferred can rupture one of its chemical bonds, possibly severing one of the sugar-phosphate chain side rails or strands of ladderlike structure, potentially causing a point mutation; common with low LET radiation and can be fixed via repair enzymes

Point mutation

can result from a single-strand break; a genetic change that occurs when a single base pair in a DNA or RNA sequence is altered, either by adding, deleting, or substituting a base

double-strand break

further exposure of DNA to radiation may result in more breaks in chains; may be repaired but not as easily; if not repaired, further separation may occur threatening the life of the cell; occurs more frequently with high LET radiation

Double-Strand break in same rung of DNA

2 direct hits on DNA, one on each side of the chain that occur within the same rung and result in a cleaved or broken chromosome with each new portion containing an unequal amount of genetic material; if cell divides, results in unequal amount of genetic material to daughter cells which results in impaired cell function or cell death

Mutation

loss or change of base in DNA chain

Covalent cross link

chemical unions created between atoms by single sharing of one or more pairs of electrons; can create sticky molecules that can cause them to be stuck to other macromolecules or other segments of same chain; these are potentially fatal if not repaired

Metaphase and Anaphase

During which mitosis phases can radiation-induced chromosome breaks be viewed microscopically?

Metaphase

During which phase of cell division are cells the most radiosensitive?

chromosomal fragments

After chromosome breakage, _______________ are produced and each fragment has a fractured extremity with sticky ends, which results in fragments rejoining in original configuration, failing to rejoin and instead create a lesion or anomaly, or region other broken ends and create new chromosomes that may not look altered

Chromosome Aberrations and Chromatid Aberrations; which type is determined on whether it occurred before or after DNA synthesis

What are the 2 types of chromosome anomalies? How do they differ?

Chromosome aberrations

Type of chromosome anomaly that results when radiation occurs before DNA synthesis takes place; results in both chromatids exhibiting breaks; each daughter cell inherits a damaged chromatid as a result of failure in repair mechanism

Chromatid abberations

Type of chromosome anomaly that results when irradiation occurs later in interphase after DNA synthesis has occurred; only 1 chromatid breaks so only 1 daughter cell affected

2; 1

With Chromosome aberrations, how many daughter cells will inherit a damaged chromatid? With Chromatid aberrations?

Restitution, Deletion, Broken-End Rearrangement

Structural changes may result in one of the 3 types of consequences to the cell. What are they?

Restitution

type of structural change; breaks rejoin in original configuration with no visible damage

Deletion

type of structural change; part of chromosome or chromatid is lost at next cell division causing Acentric FragmentBro

Broken-End Rearrangment

type of structural change; grossly misshapen chromosome may be produced

DNA

master or key part necessary for cell survival

Instant Death

occurs when x-ray or gamma dose of about 1,000 Gy (100,000 Rad) in second or minutes hits cell

Reproductive Death

occurs due to dose of 1-10 Gy (100-1,000 rad) to cell results in cell not being able to procreate; doesn’t kill cell

apoptosis

occurs when cells die without attempting division; occurs spontaneously in normal tissue and tumors; may be instigated by radiation but governed by cell radiosensitivity

Mitotic death

when a cell dies after 1+ divisions

Mitotic Delay

a delay in cell division, can be caused by as little as 0.01 Gy (1 rad); after delay, cell can divide normally

Interference

with function; can be permanent or temporary

Chromosome breakage

when x-rays interact with DNA causing breaks in the side rails or rungs of ladder

Cell Survival Curves

What can be used to display cell radiosensitivity?

Skin Erythema Dose (SED)

What used to be used to measure radiation exposure (dose it took to make skin red)?

Basal cells of skin, blood cells (lymphocytes and erythrocytes), intestinal crypt cells, reproductive (germ) cells

List the most radiosensitive/least radioresistant cells

Brain cells, muscle cells, nerve cells

List the most radioresistant/least radiosensitive cells

0.25 Gy (25 Rads)

Radiation depresses number of cells in peripheral circulation; Whole body dose of ____________ produces measurable depression

3-4 Gy (300-400 Rads)

A whole body dose in excess of ____________ may cause death within 30-60 days in humans. This is the LD 50/60

Lymphocytes

These are the MOST radiosensitive/least radioresistant cells in the body

Adult Nerve Cells

These are the LEAST radiosensitive (most radioresistant) cells in the body

2 Gy (200 Rad); 5-6 Gy (500-600 Rad)

____________ dosage may cause temporary sterility for up to 12 moths in male spermatogonia while a dose of ____________ may cause permanent sterility (threshold dosages)

2 Gy (200 Rad); 5 Gy (500 Rad)

____________ dosage may cause temporary sterility in females while a dose of ____________ may cause permanent sterility (threshold dosages)