Radiation Biology

Stochastic effect

Random/chance effect

Stochastic dose relationship: Dose __ → probability _ ; severity (does/doesn’t) increase with dose

Increases, Increases, Doesnt

Main stochastic effect in diagnostic imaging

Radiation-induced cancer

Deterministic effect / tissue reaction

Radiation effect with a threshold; once exceeded, severity increases as dose increases

Deterministic dose relationship

Threshold must be crossed → higher dose causes greater severity

Deterministic examples

Skin erythema, epilation, cataracts, and decreased sperm count

Skin erythema threshold

About 2 Gy or 2,000 mGy

Epilation threshold

About 3 Gy or 3,000 mGy

Sperm depression threshold

About 100 mGy

An electron is knocked out of an atom, producing a positive ion and a free electron

Ionization

Why an atom becomes a positive ion after ionization

It loses a negatively charged electron

The positive ion and free electron produced by the same ionization event

Ion pair

Important biological effects occur when radiation damages a sensitive cellular target, especially DNA

Target theory

Most important cellular target for radiation damage

DNA

Radiation directly interacts with and damages DNA

Direct action

Direct action can be caused by

An x-ray photon or energetic/free electron directly interacting with DNA

Radiation interacts with water first; reactive products then damage DNA

Indirect action

Why indirect action is more common with x-rays

More water than DNA

Ionization/decomposition of water caused by radiation

Radiolysis

Radiolysis of water produces ____ ____ that may damage DNA

free radicals

Highly reactive molecule or atom with an unpaired electron that can damage cellular molecules

What are Free radicals

Direct vs indirect action

Direct = radiation → DNA; Indirect = radiation → water → free radicals → DNA

Common DNA injury that is usually relatively easy for the cell to repair

Base-pair lesion

One DNA strand is broken; usually easier to repair because the opposite strand can serve as a template

Single-strand DNA break

Both DNA strands are broken; more difficult to repair correctly and more likely to cause serious damage

Double-strand DNA break

Double-strand break

Most serious DNA break

Effect that appears relatively soon after exposure, usually within hours, days, or weeks

Early radiation effect

Skin erythema, epilation, and decreased sperm count

Examples of early radiation effects

Effect that appears months to years after radiation exposure

Late radiation effect

Cancer, leukemia, and cataracts

Examples of late radiation effects

Time between the radiation exposure and appearance or diagnosis of the radiation effect

Latency period

About 5–7 years

Approximate leukemia latency from Clover

About 10–60 years

Approximate solid-tumor latency from Clover

Illness caused by a very large radiation dose delivered to most or all of the body over a short time

Acute Radiation Syndrome (ARS)

Deterministic effect with a very high threshold

ARS is what type of radiation effect with what type of threshold?

1 Gy; 10 Gy; 50 Gy

ARS syndrome dose ladder Hematopoietic ≈ ___ Gastrointestinal ≈ _ . Cerebrovascular ≈

Bone marrow destruction → inadequate blood-cell production → infection and hemorrhage

Hematopoietic syndrome

Why hematopoietic syndrome occurs at the lowest ARS dose

Bone marrow and blood-forming cells are highly radiosensitive

Destruction of intestinal lining → severe diarrhea, dehydration, and electrolyte imbalance

Gastrointestinal syndrome

Extreme radiation dose damages brain/vascular structures → neurologic symptoms, convulsions, coma, and rapid death

Cerebrovascular syndrome

ARS phases in order

Prodromal → Latent → Manifest illness → Recovery or death

Early initial symptoms that can begin minutes to days after exposure

Prodromal phase

Temporary period when the patient may appear to improve even though radiation injury remains

Latent phase

Full clinical syndrome appears; higher dose generally causes more severe symptoms

Manifest illness phase

Dose expected to kill 50% of an exposed population within 60 days

LD50/60

Approximately 3–4 Gy whole-body dose

Human LD50/60 from Clover

Most radiosensitive cells are immature, unspecialized, and rapidly dividing

Law of Bergonié and Tribondeau

Developing fetal cells are immature, unspecialized, and rapidly dividing

Why embryo/fetus is radiosensitive

Developmental abnormality caused by an exposure during pregnancy

Teratogenic effect

About 1–10 days; main concern is lethal all-or-nothing effect

Pre-implantation period

About 10 days–6 weeks; main concern is congenital malformations and growth abnormalities

Organogenesis period

Fetal period

About 6 weeks–birth; main concern is cerebral/CNS developmental effects such as reduced IQ and microcephaly

Approximate fetal-effect threshold from Clover

About 100 mGy

Embryonic/fetal timeline memory

1–10 days = death/all-or-nothing; 10 days–6 weeks = deformity/organs; 6 weeks–birth = brain/development

Radiation-induced carcinogenesis

Radiation damages DNA → incorrect repair/mutation → mutated cells may proliferate uncontrollably → cancer

Why radiation-induced cancer is difficult to identify

Long latency, stochastic probability, and it looks histologically like cancer caused by other factors

Assumes any radiation dose above zero carries some cancer risk and risk increases linearly with dose

Linear non-threshold (LNT) model