Exam #3 - Radiation Biology Notes

CELL SURVIVAL MODELS:

Target theory - is the oldest and most well-developed theory

Assumptions for the target theory -

  1. Quantal theory of energy transfer

    • radiation energy transferred in discrete “packets” = quanta

  2. Biological effect of radiation is a function

    • not the total energy absorbed

  3. Ionization of molecules in a cell is a random process

Linear quadratic -

Only 2 parameters are used: alpha and beta

→ both of these constants are intrinsic properties of the cell and can’t be manipulated

Equation:

S = e-(alphaD + betaD²) or ln S = -(alphaD + betaD²)

TARGET THEORY:

Based on the idea that there are critical sites or regions in the cell called targets that control vital cellular functions

  • targets CANNOT be defined nor will these whores ever be

It is given 3 parameters:

  1. D0 - dose of radiation needed to inactivate 63% of the cells

  2. n - extrapolation number, an idea of how broad the shoulder region is

  3. Dq - quasithreshold dose gives an idea of how wide the shoulder is

Bitch, you better memorize these three at the top unless you wanna fail like a loser omfg ^^^

MODIFIERS OF CELLULAR RESPONSE:

Cell modifiers are grouped into 3 categories -

  1. physical factors

    • ex: dose rate

    • hyperthermia

    • LET

  2. chemical factors

    • ex: oxygen effect

    • chemical sensitizers

    • chemical protectors

  3. biological factors

    • ex: cell cycle

    • fractionation

- Radiation and hyperthermia complement each other because death from heat is independent of mitosis

→ S-phase cells are resistant to radiation and are sensitive to heat.

Oxygen increases the production of free radical

  • it “fixes” free radical damage which inhibits repair

There are two categories of clinical interest:

  1. halogenated pyrimidines - direct action

  2. hypoxic cell sensitizers - indirect action

*A known gold standard of radioprotection is called Amifostine

How do you know what dose to give?

  • radiobiological principles derived from preclinical data

  • radiobiological parameters derived from clinical altered fractionation protocols

Why would you fractionate a dose?

  • produces better tumor control

    → takes advantage of the 4R’s of radiotherapy

What are the 4R’s of radiotherapy:

  • repair of sublethal damage

  • reassortment of cells within the cell cycle

  • repopulation

  • reoxygenation

Equation:

Dose Reduction Factor (DRF) = dose to get a biological effect with protector/dose to get a biological effect without a protector

Sensitizer Enhancement Ratio (SER) = dose to get a given biological effect without the sensitizer/dose to get a given biological effect with the sensitizer

TISSUE RADIATION BIOLOGY:

3 types of cells found in tissues:

  1. differentiated cells

  2. undifferentiated cells

  3. transit cells

3 basic types of tissue:

  1. static

  2. conditionally proliferative tissue

  3. proliferative tissue

Static tissues -

advantage: no need to provide a way to replace the cells

disadvantage - any damage resulting in cell loss is permanent

→ Ex: central nervous system

Stem cells meet the need in what 3 ways?

  1. stem cells can differentiate

  2. they can undergo rapid and extensive proliferation to provide supplies of cells

  3. they’re capable of long survival due to self-renewing and don’t deplete their numbers

What are the factors effecting radiation response?

  • degree of cell proliferation

    → law of Bergonie and Tribondeau

  • state of differentiation of a tissue

  • type of cells in a tissue

  • tissue organization

Damage to tissues can be classified in two ways:

  1. acute damage

    • show damage earlier

    • proliferative tissue

    • gets better with time

  2. late damage

    • doesn’t get better with time

    • progressive

    • shows damage after treatment

3 categories of assays:

  1. clonogenic assays - assay the stem cell component of a tissue

  2. functional assays - used for tissues that don’t have a well-defined stem cell component

  3. lethality assay - most often used for tissue

    → lethal dose to 50%

RADIUM GIRLS READING ASSIGNMENT:

  1. What was the name of the lawyer who took Katherine Schaub and Grace Fryer’s case? What was his agreed upon compensation?

    • Raymond Berry, and he contracted to take a split of one-third of the compensation before agreeing to just a quarter

  2. What was the deal that Dr. Knef tried to make with the USRC?

    • he wanted to be compensated for the free treatment he gave to the girls and said he would keep quiet if they gave him $10,0000

  3. What evidence did Dr. Flinn miss that the dial painters’ illnesses went beyond the Orange Plant and were caused by their occupation?

    • He missed examining Elizabeth Dunn or her former colleague named Frances Splettstocher since they’d be crucial evidence that the illness went beyond the Orange Plant