Radiation Injury

Target of Radiation Damage is DNA

experiment: expose cytoplasm and nucleus to high doses of radiation Þ only nuclear exposure dies

chromosomal damage: before replication (i.e. dicentrics and rings)

chromatin damage: only one strand damaged (i.e. anaphase bridge)

DNA damage can lead to cell death when division attempted, oncogenesis, mutations in subsequent generations (if in germ cells, mutations passed on)

Ionizing radiation – interacts with matter to produce fast electrons

Compton effect: radiation reacts with outer shell e^- to produce high energy e^- and photon

Photoelectric effect: radiation reacts with inner orbital e^- to produce high energy e^-

another e^- drops in energy level to fill space and characteristic x-ray is emitted
low energy as in diagnostic radiology; process predominates at low energies

High energy electrons (fast electrons) cause damage to nucleus in two ways:

(1) Direct – fast electron or ionizing radiation (neutron) interacts directly with DNA (1/3 of damage)

(2) Indirect – ionizing radiation or fast electron interacts with water to produce hydroxyl radical Þ DNA damage (2/3)

Cellular Susceptibility

rapidly dividing cells more susceptible

most susceptible in M and G₂ phases

most resistant at end of S phase

damage enhanced by the presence of oxygen: can ‘fix’ damage so it cannot be repaired by producing an organic peroxide

OER (oxygen enhancement ratio): dose without oxygen / dose with oxygen = 2.6-3 for x-rays

Four R’s that affect susceptibility to radiation damage:

(1) Repair – sublethal damage can be repaired; rad therapy given in split doses to allow normal tissue repair

(2) Reassortment – mostly cells in sensitive phase die, resistant phase cells remain Þ reassort to all phases

(3) Repopulation – both tumor and normal cells will regrow between doses

(4) Reoxygenation – peripheral cells of tumor are well oxygenated and are killed first

Þ hypoxic cells at center are then reoxygenated and more sensitive to the next dose

Clinical Manifestations of Acute Radiation Syndrome

Category	Whole Body Dose	Symptoms	Prognosis
Subclinical	< 200 rem	mild nausea, vomiting neutrophil/platelet(1500/mm²)	100% survival
Hematopoitic	200 - 600 rem	nausea, vomiting, hemorrhage min neutrophil/platelet count in 2 weeks (1000/mm²)	infections possible marrow transplant needed
Gastrointestinal	600 - 1000	severe nausea, vomiting, death severe neutrophil/platelet depression hemorrage and infection in 1-3 weeks neutrophil/platelet(500/mm²)	shock and death within 10-14 days
CNS	> 1000	intractable nausea, vomiting confusion, convulsions, coma lymphocytes absent	death in 14 - 36 hours

effect on growth and development: effect on fetus or child varies with time of exposure and with dose

late tissue effects: varies with type of tissue, dose, volume of tissue exposed

Radiation Oncology

used to treat malignant and benign tumors

external beam radiation

brachytherapy (implants)