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47 Cards in this Set

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What causes detectible changes, damage and cell kill?
Depletion of critical Target cells
What factors determine the response of a tissue/organ to radiation?
1. Inherent sensitivity of the cells in that tissue.

2. The turn over kinetics of each cell population in the tissue
Tweo factors
Why do normal tissues vary in their response to radiation?
What needs to be taken into account are the various cell populations, do they divide, and if so how often
Who first started to identify some cell lines that appeared to be more sensitive than others?

What did they see?
Bergonie and Tribondeau - in 1906

1. X-rays appeared to destroy the cells of malignant neoplasms without permanently harming the adjacent healthy tissues

2. Some tissues were damaged by doses of radiation that did not appear to harm other tissues
What animal organ was used for the first experiments in tissue damage?

Why?
Rodent testicles

They contained at least two very different cell lines
What cell types do rat testicles contain?
A mature differentiated highly specialized spermatozoa

Immature rapidly dividing undifferentiated spermatogonia
Two types
Which cell types were more radio sensitive?
Immature dividing cells were more radiosensitive than mature non-dividing cells.
What factors amke the cells the most radio-sensitive?
The most radiosensitive cells were those which:

are the most immature.

are the least specialized.

have the greatest reproductive activity.

have the longest mitotic phase.
Four factors
Who modified the earlier hypothesis on cell sensitivity?

What was added?
Amcel and Vitemberger - 1925

They stated that the inherent sensitivity to radiation damage is the same in all cells, BUT that the TIME of the appearance of radiation induced damage differs among different cell types
What did Amcel and Vitemberger state that influenced the appearance of cell damage?
1. - The BIOLOGICAL STRESS placed on the cell.

The most important biological stress placed on the cell is the necessity for division.

All cells would be equally damaged by a dose of radiation , but that damage would be expressed only if and when the cell divided.

Cells that divide sooner express damage sooner and appear more radiosensitive.

Cells that divided more slowly would appear more radioresistant.

2.- CONDITIONS to which the cell is exposed both PRE and POST irradiation.

An example would be PLDR.
Two main items
What is the Kinetics of cell turnover dependent on?
Kinetics of cell turnover (how fast) is dependent on: cells entering, cells leaving and cells dividing in a tissue or organ
Define Differentiated cells.
Differentiated cells: specialized functionally and or structurally, considered to be mature or end cells.
Define Undifferentiated cells.
Undifferentiated: immature, not specialized, considered precursor or stem cells.
Give examples of Differentiated and Undifferentiated cells.
Fully differentiated

Spermatozoa- mature, non-dividing cell, structurally and functionally specialized

RBC- erythrocyte- this is a mature red blood cell- fully differentiated and specialized in function and structure ( transport oxygen/ non nucleated).

Un-differentiated cells

Spermatogonia –immature, their only function is to divide. These represent the stem cell population

Erythroblast- these are in the bone marrow- undifferentiated, stem cell for the erythrocyte
What are the 3 main populations of cells?
Stem cells

Transit cells

Static populations
What is the sole purpose of stem cells?
Stem cells- sole purpose is to divide:

1. To maintain its own population (self-renewal).

2. Produce cells for transit or static populations.
Give examples of Stem cells.
Basal cells

bone marrow

crypts of lieberkuhn

spermatogonia
What special capacity do Tissues/Organs with stem cell populations have?
Tissues/Organs with stem cell populations are self renewing.
What are Transit cells?
Cells on their way from the stem cell compartment to an end cell compartment.

The nucleated red blood cell divides in transit
What are Static cells?
They lose cells throughout life of the tissue or organ, these are fully differentiated cells, with little or no mitotic activity.

Adult nervous tissue and muscle tissue
What are the categories of cell radiosensitivity?
1. Vegetative intermitotic cells (VIM), rapidly dividing, undifferentiated, with a short life span.
Basal cells, type A spermatogonia, crypt cells, erythroblasts.

2. Differentiating intermitotic cells (DIM), produced by the division of VIM cells, more differentiated but still very active mitotically.
Intermediate type B spermatogonia, and myelocytes.

3. Multipotential connective tissue cells (stromal components). These divide irregularly, intermediate in radiosensitivity.
Endothelial cells, fibroblasts, and osteoblasts

4. Reverting post mitotic cells (RPM), normally don’t divide, but can under special circumstances, long lived and relatively radioresistant.
Liver cells and mature lymphocyte.

5. Fixed post mitotic cells (FPM), these cells do not divide, are highly differentiated both structurally and functionally. The most resistant to radiation.
Adult nerve cells, erythrocytes, muscle cells, spermatozoa.
What are Target cells?
Target Cells- are the cells that can divide and regenerate the tissue (Stem Cells).
What are the two compartment types of tissues?
1. Parenchyma – cells that perform the function of the organ.

2. Stroma – cells that make up the supporting network of the organ. These include vascular and connective tissue.
Give examples of organs with only RPM or FPM cells.
Liver (RPM) and the Brain/Spinal cord (FPM’s)
Give examples of organs with VIM, DIM and FPM cells.
Skin

Intestinal tract

Testes.
What is the mechanism of tissue and organ damage?
The response in all tissues and organs is due to the direct killing of the parenchyma cells

Some organ damage just takes longer to show up

Damage is seen in the intestine within 10days, but not in the lung for 3 months.
Into what divisions may all tissues and organs be classified?
1. Acutely responding.

2. Late responding.

This refers to the time it takes for damage to appear or occur
Two categories
What is Acutely Responding tissue?
Acutely responding tissue(early responding). Manifest injury within a few weeks to months after completion of radiation

This happens with self-renewing tissues such as bone marrow, intestinal lining and testes.
What is Late Responding tissue?
Late responding tissue – does not express injury for at least 3 months or longer, these tissues contain slowly dividing cell populations

The lung and kidney are examples of late responding tissue/organ.
What are Assay systems?

What must they must be able to produce?
Used to compare and contrast response of differing tissues to radiation

Must produce the following 2 results.

1. Damage must be a function of dose.

2. Damage must be quantifiable.
Two results
What must Assay Systems show?
The assay system must show that as dose increases, the effect, outcome or damage must also increase. (It is a function of dose).

The data must be quantifiable, meaning that some system of numbering the damage can be applied to the damage seen
What are the types of assay systems used?
Clonogenic

In situ

Transplantation

Functional

Lethality
Which three Assay systems are the same in function?
Clonogenic

In situ

Transplantation
What does a Functional Assay system evaluate?
The working capacity of the organ.
What do Lethality studies evaluate?
Lethality studies are done on animals to see how many survive.
What does the term Clonogenic mean?
Clonogenic refers to stem cell populations that are able to divide and form clones in vivo.
Where is an In Situ Assay conducted?

For which tissues have they been developed?
Studied in the body

Kkin, intestine, testis and kidney
What causes damage in the kidneys?
Damage in the kidney is due to depletion of epithelial cells lining the proximal tubules
When would an In Situ assay be done on a kidney?
Assays for late responding tissues are taken at 1 year out

Kidney tissue is well differentiated and divides very slowly
What is a transplantational Assay?

What types of tissue require this?
The irradiated tissue be removed from the animal

A single cell suspension is then made and injected into another animal

The recipient animal acts like a culture dish

Bone marrow, thyroid and mammary glands
What must first be done to a recipient animal before a Transplantational assay can occur?
The syngenic recipient animal must be previously irradiated

So that all the cells being studied are destroyed in the recipient
Why can only a Functional assay be performed on some tissue?
Many tissues do not have clonogenic stem cells that can be readily identified and quantified, particularly those tissues classified as late responding
How is the data presented differently for Functional assays?
It is represented using dose response curves rather than cell survival curves
What are the different types of Functional assay tests?
These tests are based on changing physiology of the organ, (breathing rate measurements, urine output measurements)

Or they rely on scoring visible changes in the organ (acute skin reactions, loss of hair, desquamation)
What is observed in a Lethality assay?
The number of dead animals after a localized irradiation of a specific organ is quantified, as a function of dose, and dose response curves are created.
What is the definition of LD50?
the lethal dose that kills 50% of the animals is obtained for different tissues. Allowing for comparisons of the dose for this same effect called ISOEFFECT between tissues
How is the LD50 further defined?
The LD50 for a given tissue is further defined by the time when death occurs