MEDRADSC 2X03 - Lecture 7 - Cellular Radiosensitivity

division delay

disturbance to cell cycle activity

what are the two types of lethal damage to a cell through irradiation?

apoptotic and mitotic death

what are the two types of non-lethal damage?

reparable and non-reparable

cell cycle time

the time required to complete one cell cycle

how long does it take to complete mitosis?

about one hour

how long does it take to complete S phase of interphase?

about fifteen hours

mitotic index

fraction of cells in mitosis

what are the main difference between in vitro and in vivo cells?

in vitro cells can be produced to be synchonous, where in vivo cells are normally asynchronous and is in all cell cycles

what happens to a mitotic cell post-irradiation?

there is a mitotic delay, in which mitosis freezes, and then there is a mitotic overshoot which functions to compensate for the delay

where are the two points at which division delays occur in the cell?

G2 and early S phase

G2 checkpoint

checks cells which are about to enter mitosis

S checkpoint

checks cells which are about to enter DNA synthesis

what checkpoint is the MAIN contributor to division delay?

G2

when is the cell MOST radiosensitive?

M phase

why does mitotic overshoot occur?

due to synchronizing effect of radiation

what does dose effect in terms of division delay?

magnitude of decrease of mitotic index, length of the delay and the size of the overshoot

what happens to the mitotic index post irradiation at low doses?

mitotic index returns to normal

what happens to mitotic index post irradiation at high doses?

delay occurs but there is lethal damage

what are the two methods of obtaining synchronized cell populations?

mitotic harvest and drug-induced G1 hold with hydroxyurea

what does the cell survival curve look like for cells irradiated at M, later G2?

no shoulder, steep slope & repair is unlikely

what does the cell survival curve look like for cells irradiated at early S?

noticeable shoulder, less steep slope and repair of sublethal damage will occur

when is the least sensitive phase of the cell cycle?

late S, due to homologous recombination

There is a sharp ______ in sensitivity from the start to the end of G2.

increase

what two phases does the sensitivity change over the duration of its events?

G1 and G2

what is the effect of different types of radiation on the various radiosensitive phases of the cell cycle?

there is no effect on the timing of sensitivity, rather the magnitude of difference in sensitivity

what is the difference between high LET and low LET radiation in terms of their variation of radiosensitivity across the cell cycle?

high LET there is less variation, low LET there is more SSBs than DSBs, and as a result is more easily repaired

According to Bergonie-Tribondeau's hypothesis, radiosensitivity is highest in cells that:

are actively dividing, are undifferentiated and have a long future of dividing

"the response of the ____ is more clinically significant than response of the ____ alone."

A. cell, tissue

B. tissue, cell

C. organ, tissue

D. tissue, organ

B

what are the three factors that mainly effect tissue response to radiation?

inherent sensitivity, structural organization and tissue kinetics

what are the five categories in Casarett's Classification of Cell Radiosensitivity?

From most radiosensitive, to most radioresistant:

1. Vegetative Intermitotic Cells (VIM)

2. Differentiating Intermitotic Cells (DIM)

3. Multipotent Connective Tissue Cells (MCT)

4. Reverting Post-Mitotic Cells (RPM)

5. Fixed Post-Mitotic Cells (FPM)

what is an example of a VIM cell?

stem cell

what is an example of a DIM cell?

spermatogonium

what is an example of a FPM cell?

muscle cell

what type of cell is an exception to Casarett's Classification?

lymphocytes, structurally they are RPM, but they die from apoptosis and are the most sensitive cells