Chapter 14 Flashcards

1
Q

Define ionizing radiation.

What energy must a photon have to be considered ionizing radiation?

A

Xrays (for example) are one type. Results when a photon has sufficient energy that when it interacts with an electron it displaces the electron from its orbit around the nucleus of the atom, thereby leaving the atom with a net positive charge.

Must have > than 10 electron volts.
(2-10 eV is non-ionizing such as UV light)

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2
Q

Xrays are produced when electrons are accelerated and hit a ____ target. As they decelerate they emit a spectrum of bremstrahlung radiation.

When xrays interact w/ tissue they give up energy by 1 of 3 processes. Name the 3 processes in order from lowest to highest energy.

For the lowest and middle energy process, describe where in clinical practice these are used.

A

Tungsten
Photoelectric, Compton, Pair production
Xrays for dx purposes + RT for tx (respectively)

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3
Q

Describe brachytherapy

A

Delivers highly localized RT dose from w/in an organ or tissue using implanted wires or seeds containing radioisotopes such as I125 that undergo radioactive decay

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4
Q

Describe skin sparing, what does it mean?

With what types of energy/treatments do we see skin sparing?

A

With high energy xray beams the beam is less attenuated by the skin surface. Most of the energy is then deposited at some depth into the tissue bc it takes time for ionizations to occur and for the dose to reach electronic equilibrium.

No skin sparing seen w/ low energy RT beams (50-250 keV such as w/ orthovoltage). We see skin sparing w/ photons and electrons.

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5
Q

Radiation dose is measured in terms of the amount of energy absorbed per unit mass known as ____ per kg which are more commonly referred to as _____.

A

joules

gray

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6
Q

Energy is deposited in matter along its track. Particles lose energy proportional to their energy and depends also on the particle’s velocity, charge (Z), and density of the target.

This concept is known as _______. The amount of energy lost or deposited (varies or is constant) along the path.

A

LET - linear energy transfer.
Varies - as it slows down, it loses energy more and more rapidly until it reaches a max rate of energy loss known as the Bragg Peak.

High LET RT has less deflection and sharp Bragg peak dt peak energy deposition at the same position in tissue (14.2). Ex: neutron, proton

Low LET RT has a lot of deflection and t/f LET varies along the track.

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7
Q

Radiation damage w/in cells occurs via either direct or indirect damage. Define both types and state which is more common.

A

DIRECT -
energy absorption occurs directly from the RT beam (ionizing RT) ie photon excites electron which causes DNA damage

INDIRECT -
energy is transferred from 1 molecule to another causing damage. *MOST COMMON. Specifically, most energy is absorbed into water leading to production of reactive intermediates such as OH dot (hydroxyl radical) which damages the cell. ie photon excites electron which produces free radicals after interacting w water and free radicals cause damage

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8
Q

Name some (at least 2) natural free radical scavengers in the body.

A

Thiol compounds (contain SH - sulfhydryl groups) ex glutathione, cysteine
Vitamine C and E
Superoxide dismutase

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9
Q

Name a thiol containing drug used as a radioprotective agent.

A

Amifostine

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10
Q

The main target for RT induced damage is ____. Often many different types of damage occur in one area of the cell.

What type of damage is the least likely to be repaired?

Name the histone protein marker that is phosphorylated when this damage occurs and can be quantified as an intracellular marker of this type of damage.

A

DNA
double strand breaks (# of unrepaired dsDNA breaks correlates w/ cell lethality)
H2AX - histone protein

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11
Q

Chromosomal rearrangements can occur at the first mitosis after RT damage of DNA.

Two methods by which cells repair DNA ds breaks include:

A

Non-homologous end joining and

Homologous recombination

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12
Q

Describe the bystander effect

A

Some factors that perpetuate an unstable phenotype include the continued production of reactive O2 species. These can be released from irradiated cells and cause damage to neighboring non-irradiated cells (bystander cells). Can lead to total cell kill w/in an irradiated cell population that is greater than that calculated based on the # of cells that were indirectly irradiated or effected by the RT.

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13
Q

UV radiation can also cause DNA damage.
Is UV RT ionizing or non-ionizing?
UV RT deposits energy in selected molecules resulting in excitation of ____ that can react w/ water to form ___.
Reactions bt these mols and other cell mols can occur and result in DNA protein crosslinks. Cells in which phase of the cell cycle are most resistant to UV damage?

A

UV is NON ionizing
pyrimidine bases (T or C)
Pyrimidine dimers (production linear w/ dose) formed in all phases of the cell cycle
Most resistant in LATE S (increased sensitivity in G1 through early S)

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14
Q

A tumor is controlled if its stem cells are prevented from continued proliferation. A cell that survived tx w/o losing this ability is stated to be able to form a clone.

Describe the clonogenic assay that is the mainstay of radiobiology research.

A

Tumor cell suspension is plated. Some are not treated and after a few days colonies are counted. Other cells are plated and irradiated to see how many can form a colony after RT. Used to determine how many more cells die post RT and t/f to create a survival curve. A colony is defined as >50 cells (6 cell divisions). Normal plating efficiency even w/o RT is bt 0.5 and 0.8 meaning 50-80% of cells initially plated will survive to form a colony even w/o RT.

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15
Q

Draw a typical cell survival curve for cells tx w/ gamma or xrays (low LET) and another for high LET RT (neutrons).

Label x and y axes.

A

p271 - 14.9 and 14.10

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16
Q

Describe the relative biological effectiveness

A

The ratio of the dose of a standard type of RT to that of the test RT that gives the same biological effect

17
Q

The LINEAR QUADRATIC model of cell kill is the most favored model currently used to explain cell killing after RT exposure. It includes that multiple lesions, induced by RT, must interact in the cell to result in cell death. There are 2 parts to the survival curve whose slopes correlate w/ repairable and non-repairable damage. These are described as alpha and beta. Which of alpha and beta correlates w/ repairable and which w/ non-repairable damage?

A
ALPHA = non-repairable
BETA = repairable

Alpha the shoulder varies a lot bt different types of mammalian cells, this is the clinically relevant dose. Beta is the same for most mammalian cells but this is at high dose which is often not clinically relevant

18
Q

After tx w/ RT cells can undergo terminal growth arrest (senescence), undergo interphase death, or lysis during apoptosis, or mitotic catastrophe.

Which is most common cause of death in normal and tumor cells?

Lymphocytes alternatively, undergo what type of death?

A

Mitotic catastrophe

Apoptosis

19
Q

What are the 4 Rs of RT? Describe each.

Which is responsible for the fact that tissues can tolerate a higher total dose if divided into smaller fractions?

A

Repopulation
Reoxygenation
REPAIR
Redistribution

20
Q

The shoulder of the cell survival curve indicates what?

A

This is the part of the survival curve that reflects accumulation of sublethal damage that can be repaired

21
Q

Cells that survive a single RT treatment tend to be synchronized in the same phase of the cell cycle. If irradiated 2h post chemotherapy, (more or less) cells survive the second treatment because they are in the more (sensitive or resistant) phase of the cell cycle?

A

MORE

resistant

22
Q

Cells in different phases of the cell cycle respond differently to RT exposure. After RT exposure the # of cells in mitosis (increases or decreases)? Why does this occur?

A

Decreases.
Both lethally damaged cells and surviving cells stop entering mitosis and cells in mitosis continue through cell cycle progression (remember once cells enter mitosis they cant stop progression). After a while, surviving cells re-enter mitosis (known as mitotic delay) which occurs largely dt a block of cells in G2 phase.

23
Q

In what phase of the cell cycle are cells most sensitive to RT? Most resistant?

A

Sensitive -G2/M transition

Resistant - Late S

24
Q

Name a protein that plays an important role in checkpoint pathways in all 3 cell cycle phases

A

ATM (ataxia telangiectasia mutated) - nb at G1/S bc it leads to continued hypophosphorylation of Rb, S phase checkpoint, G2 checkpoint

25
Q

Name 2 pathways nb in repair of ionizing RT-induced DNA damage

A

BER
DNA ds break repair (primarily w/ HR in S phase and G2)
NHEJ in G1

26
Q

Constitutive activation of Ras can lead to RT resistance. How is Ras constitutively activated? Name a category of drugs that can inhibit this and lead to increased RT sensitivity.

A

Ras when mutated is permanently activated in GTP-bound signaling state providing proliferative signals in the absence of GF ligands leading to altered cell growth and radioresistance.

Farnesyl transferase inhibitors can inhibit this and lead to increased radiosensitivity

27
Q

Name at least one other pathway that can lead to tumor radioresistance aside from Ras

A

RAF-MEK-ERK

P13K-AKT-PKB, also by increased IGFR1, EGFR, Her-2