Rad 102 Lecture 8 Definitions

W-value

Mean energy required to form an ion pair in a given material

Whats an ion pair?

Formed when electron is kicked from an atom (due to ionization) and produces two oppositely charged particles

Whats produced from an ion pair?

Cation (+): atom/molecule that lost the electron

Anion (-): the freed electron

What is specific ionization (SI)?

How’s it determined?

The number of ion pairs produced per unit distance

Determined by combining LET with the W-value

Whats the W-value for tissue?

34 eV/ion

Define LET

Linear Energy Transfer

• Energy absorbed by material per unit distance

How do we determine radiation/something is dangerous?

• Epidemiology

• Biologic Mechanism

What is epidemiology?

Evidence of detrimental/harmful effects in an exposed population

What is Biological Mechanism

Evidence of a deleterious/harmful reaction in a living organism

What are the 4 exposed populations?

• Early radiation workers

• Atomic bomb survivors

• Nuclear accidents

• Patients

What are the modern workers of radiation?

• Researchers/ Scientists

• Nuclear Industry Workers

• Radiologists

• Technologists

Observed effects in Nuclear Bomb Survivors

1. Immediate Effects: Acute Radiation Syndrome

2. Teratogenic Effects: Harm to developing fetus during pregnancy

3. Mutagenic Effects: causes mutation (change in cellular DNA)

4. Long-term Effects: significantly increases cancer

What are 2 severe nuclear accidents, and what year did they occur?

Chernobyl (1986)

Fukushima Daiichi (2011)

Medical patients / Early medicals studies using radiation

• Ankylosing Spondylitis: rad therapy to spine

• Postpartum Mastitis Study: breast tissue

• Thorotrast: x-ray contrast material containing torium

• Cancer Patient

  • Oncology patients (rad therapy)

  • Hyperthyroidism (iodine-131)

  • Bone Marrow Transplants

problems with epidemiological collection

• Very high exposures

• Acute exposure vs. Chronic exposure

• Dose usually NOT measured

• NOT representative

Primary target of radiation damage? What can it cause?

DNA / Cell nucleus

• Cell death

• Cancer

Direct vs. Indirect DNA Damage

Direct: causes ionization in DNA

Indirect: interacts with intracellular DNA, produces free radicals → those attack DNA

Whats ionized in direct DNA damage

• Sugar-phosphate backbone (rails of ladder)

  • Ionization of the ONCP atoms

• Nitrogenous bases (ladder rungs/steps)

  • Ionization of the ATCG

What are the nitrogenous bases

ATCG

• Adenine

• Thymine

• Cytosine

• Guanine

Results From DIRECT DNA damage

1. Single Strand Break: of DNA backbone

2. Double Strand Break: opposite strands

3. Loss of base/bases: results in depurination/depyrimidination

What type of radiation causes DIRECT DNA damage?

High LET radiation

What type of radiation causes INDIRECT DNA damage?

Low LET

Whats ionized in INDIRECT DNA damage? Mechanism?

Water molecules of cells

• Radiolysis (ionization of water): produces free radicals (highly reactive chemical)

  • Those go on to break bonds/bases in DNA

Direct vs. Indirect DNA damage: Whats more common?

Indirect

Three states of radiation damage

• Pre-chemical stage: direct ionization & radical formation

• Chemical stage: diffusion of radicals & radical attack of DNA

• Biological stage

  • Less than 10⁻³ s: Radical reactions complete

  • Less than 1 s: Biochemical changes complete

  • Hours: Cell division affected

  • Days: Gastrointestinal and central nervous system changes

  • Weeks: Lung fibrosis

  • Years: Cataracts and cancer

Whats the bystander effect in DNA damage

Radiation can cause damage in cells NOT hit by particle

3 Categories of biologic effects of radiation

Category	What we're asking	Types
Heritability	Who is affected?	Somatic, genetic, teratogenic
Time	How long is the exposure delivered?	Acute, chronic
Dose-response	How does the effect change with dose?	Deterministic, stochastic

Describe Heritability of Damage

Somatic: effects occurring in exposed individuals own body

Genetic: effects occurring in offspring of exposed person

Teratogenic: effects that occur in exposed embryo/fetus

Describe Time to onset of biological radiation effects

Acute: high dose rate exposure over short time

• More damage

Chronic: low dose rate exposure over long time

• Less damage

Describe Dose-Response behavior

Deterministic Effect (How severe)

• Effects observed once threshold is exceeded.

• Severity increases as dose increases.

• Usually associated with higher doses and rapid onset.

Stochastic Effects (How probable?)

• No threshold dose, assume any exposure can cause effect.

• Probability increases as dose increases.

• Severity does not increase in proportion to dose.

• Often have delayed onset.

What are the four stages of ARS?

Acute Radiation Syndrome

1. Prodromal

2. Latent

3. Manifest

4. Death or Recovery

Three syndroms observed of ACS

Hematopoietic Syndrome

• Bone marrow and blood-forming tissues.

• Latency = hrs to wks

• Low mortality, recovery possible

Gastrointestinal Syndrome (GI)

• Intestinal epithelium

• Latency = hrs to days

• Death likely w/out support within 10-20 days

Central Nervous Syndrome (CNS)

• severe damage to the small blood vessels supplying the nervous system.

• Latency = hrs

• Death within hrs-days

Describe stage 1 of ARS

Prodromal

• Within hours of exposure

• Symptoms

  • NVD, fatigue, malaise

  • Blood chemistry changes (leukopenia, anemia)

  • Increased body temp

Describe stage 2 of ARS

Latent

• No visible effects or symptoms seen

• Lasts about a week

Describe stage 3 of ARS

Manifest

• Symptoms become apparent

Describe stage 4 of ARS

Death or recovery occurs.

Whats LD 50/30? Is it complicated to predict? Why?

Lethal dose for 50% of population, death occurring within 30 days

Yes

• Varying sensitivities

• Medical intervention improves survival

Another name for ARS

Radiation sickness

Radiation Erythema

• Radiation burns; skin reddening

• Latency: hrs to > 4 weeks

• Mortality depends on dose, infection risk, and treatment

Epilation

• Hair loss; depletes matrix cells of hair follicles

• Latency: 2-3 weeks

• Mortality depends on dose; temporary or permanent

Cataracts

• Clouding of eye lens

• Latency: months-decades. acute or chronic.

• Mortality depends on dose. Can be surgically repaired.

Sterility

• Inability of sexual reproduction

  • Gonads are radiosensitive

• Latency: months-years

• Mortality depends on dose, can be temporary or permanent.