Radiosensitivity

Two scientists Bergonie and Tribondeau (1906) performed experiments on the testes of rodents to determine the clinical effects of radiation (they choose the cells of the testes because they contain cells with different functions and mitotics activity)

Law of Bergonie and Tribondeau – states ionizing radiation is more effective against cells that are :

1. actively mitotic
2. undifferentiated
3. have a long mitotic future

this defines radiosensitivity in terms of mitotic activity and level of differentation.

**These two characteristics determines a normal cells sensitivity to radiation**

Cell Population

In 1968 Rubin and Casarett grouped mammalian cell populations into 5 basic categories based on sensitivity to radiation :

Tissue and Organ sensitivity

Specialized tissues and organs are made up of :

•  Parenchyma – contains characteristic cells of the tissue or organ (VIM, DIM, RPM, FPM)

•  Stroma – consists of connective tissue and the vasculature (intermediate)

**The radiosensitivity of an organ is a funtion of the most sensitive cells it contains**

Systemic Response to Radiation

Response :

Reponse to ionizing radiation treatments refers to detectable structural and functional changes that a dose produces over a certain period of time

Healing :

Organ healing can occur after radiation exposure by the process of regeneration or repair

Regeneration – refers to the replacement of damaged cells by the same cell type.   It results in partial or total reversal of early radiation changes and is likely to occur in organs containing actively dividing VIM and DIM parenchymal cells.

(ex. Skin, small intestine, bone marrow)

•  Desired healing process

•  Can return organ to its preirradiated state

Repair – refers to the replacement of damaged cells by a different cell type, resulting in a scar formationor fibrosis.

• Does not return organ to its preirradiated state
• Can occur in any organ
• More likely to occur after administration of high doses (1000 cGy and above)
• High doses deystroy parenchymal cells making regeneration impossible

General Organ Repsonse

Early or acute changes after radiation :

• Inflammation
• Edema
• Possible hemorrhaging in exposed area

Late or chronic changes (not reversible) :

• Fibrosis
• Atrophy
• Ulceration
• Tissue necrosis or death

Radiation Therapy

Goal of radiation therapy – is to eradicate the tumor while not deysroying normal tissues in the treatment field

**Radiation interaction in matter is nonspecific,   it does not distinguish between normal tissue and malignant tissue **

Fractionation Techniques :

Fractionation – treatments are given in daily fractions over a period of up to 6 – 8 weeks so that high total dose is given to the tumor while ideally sparing normal tissues.

The biological effect on tissue from fractionated radiation therapy depends on the 4 R’s of Radiation Biology :

1. Repopulation – surviving normal cells may divide leading to normal cell repopulation
2. Redistribution – we want the tumor cells in the sensitive phase of mitosis and the normal cells in the resistant phase
3. Repair of sublethal damage – normal tissue will repair itself in between   treatments.   Tumors are thought to be highly hypoxic therefore sublethal damage cannot be repaired as efficiently
4. Reoxygenation – (only applies to the tumors) process by which hypoxic tumor cells gain acces to oxygen and become radiosensitive between radiation fractions

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