Lecture 7: Radiation Safety Overview

Main-chain scission

Produces many smaller molecules; viscosity decreases.

Cross-linking

Side chains become sticky; viscosity increases.

Point lesions

Disruptions of single chemical bonds but no grossly apparent changes; primary mechanism of cellular damage from low doses of radiation over long periods.

DNA damage

Main chain scission can occur in one side rail, often quickly repaired; mis-repair possible via point mutation.

Point mutation

Change/loss of triplet code; single nucleotide is changed.

Types of point mutation

Silent - ends up coding for the same protein; Nonsense - codes for a stop codon; Missense - can be Conservative or Non-conservative.

Radiolysis of Water

Indirect effect of radiation; principle action on humans is indirect due to byproducts from the radiolysis of water.

Free radical

Byproduct of radiolysis of water; very unstable and can disrupt molecular bonds.

Hydrogen peroxide

Byproduct of radiolysis of water; very toxic.

Oxygen effect

Biologic tissue is more sensitive under aerobic conditions.

Oxygen Enhancement Ratio (OER)

OER = anoxic dose / aerobic dose; always positive.

LET (linear energy Transfer)

OER is LET dependent with an inverse relationship; greatest for low-LET.

Age risk

Highest risk is before birth; younger patients have more rapidly dividing cells and higher metabolic rates.

Law of Bergonie & Tribondeau

Greater maturity of cells increases resistance against radiation.

Radiosensitivity factors

Increased metabolic activity, cell proliferation rate, and tissue growth rate increase radiosensitivity.

Most sensitive cells to radiation

Lymphocytes, Erythroblasts, Myeloblasts, Spermatogonia/oocytes, Endothelial cells, Epithelial cells, Bones, Nerve, Brain, Muscle.

Radiosensitizers

Halogenated pyrimidines that increase sensitivity to radiation.

Radioprotectors

Contains -SH- group which competes with O2 for free radical binding; protects the patient.

Deterministic effects

Dose dependent effects characterized by a threshold dose greater than 0.5 Gy (50 rads).

Types of threshold curves

Linear threshold curve, Sigmoid threshold curve, Linear quadratic threshold curve.

Examples of deterministic effects

Leukemia, Breast cancer, Heritable damage.

Acute Radiation Lethality

The lethal dose to kill 50% of the population in about 30 days is referred to as LD 50/30.

Humans LD

The lethal dose for humans is between 300 to 400 rads.

Hematologic death

Occurs with a dose of more than 100 rads.

Gastrointestinal death

Occurs with a dose of more than 1,000 rads.

Central nervous system death

Occurs with a dose of more than 10,000 rads.

Skin

Subject to a deterministic effect; epithelial cells have moderate sensitivity.

Skin replacement rate

Skin replaces itself about 2% per day.

Epidermal basal (stem) cells

The earliest damage to the skin occurs in these cells.

Nonlinear threshold

Skin response is nonlinear with a threshold at about 200 rads.

Moist desquamation

Indicates clinical tolerance level of the patient and takes about 1800 rads over 4 weeks.

Erythema

The earliest sign of radiation injury to the skin.

SED50 for erythema

At 600 rads, about half of the population is expected to get erythema.

Fluoroscopy boost mode

Gives up to a 15 fold increase in radiation per unit time.

Standard fluoroscopy

Typically delivers 2 rads/min, while boost mode delivers 30 rads/min.

Spermatogonia

Among the most radiosensitive cells in the body.

Testes radiation effects

As little as 10 rads can decrease spermatozoa; 200 rads can cause temporary sterility.

Ovaries radiation effects

As little as 10 rads can cause delay or suppression of menstruation.

Cytogenic Phenomena

A hit usually disrupts molecular bonds and produces visible chromosomal damage.

Cytogenic Damage

Damage is usually manifest during the next cellular mitosis.

Significant radiation damage

Can cause chromosomal aberrations in the next 1 to 2 cell divisions.

Acute deterministic effect

Significant radiation damage is considered an acute deterministic effect.

Single hit

A type of cytogenic damage that occurs at very low radiation doses.

Multi hit aberrations

The most significant latent human damage that occurs at high doses, with frequency increasing when dosages increase.

Linear dose response

Slope of the relationship between dose and effect.

Absolute risk

Estimates based on the slope of linear dose response.

Excess risk

Observed cases minus expected cases.

Relative risk

Observed cases divided by expected cases.

Cataract Formation

Lens radiosensitivity that is age dependent.

Fluoroscopy

A situation where a lens shield is usually necessary.

Greater effect and shorter latent period

Observed in older age for cataract formation.

Deterministic effect

A type of effect that has a threshold.

Acute threshold for cataract formation

Probably about 2 Gy.

Fractionated threshold for cataract formation

As high as 10 Gy.

Latent period for cataracts

15 year average, but reported from 5 to 30 years.

Life span Shortening

Radiologic occupations are safe since 1965, with mortality the same as the general population.

12 days

Estimated loss of life span due to dealing with radiation.

Radiation Induced Carcinogenesis

Typically a non-threshold dose response.

Mortality below 4.0 Sv

Generally linear, except for leukemia which is linear-quad.

Radiation-induced Leukemia

Requires the least dose to develop, making it the earliest to develop.

Thyroid Cancers

Highly sensitive for radiation cancer, arising almost exclusively from follicular epithelium.

Morality of thyroid cancer

Much less (only 5 to 10%) than medullary thyroid cancer.

Natural incidences of thyroid cancer

Statistics show 4/100,000 with only 5% fatal.

Females and thyroid cancers

3x as susceptible to all types of thyroid cancers.

Increased risk for children

In their first five years.

Yellow bone marrow

Not as sensitive as red marrow.

Red marrow

Mostly found in the axial skeleton - spine, pelvis.

Yellow marrow

Mostly found in the appendicular skeleton - hand, foot.

High dose

Suppresses RBCs and lymphocytes.

Long term effects of high dose

May increase leukocyte proliferation.

Risk of leukemia from x-ray exams

As high as 12%.

Radiation-induced Leukemia Data

Linear - quadratic, non-threshold, 4 to 7 year latency (at risk for about 20 years, after which you're probably fine), 3:1 relative risk.

Solid Tumors

3 times more common than Leukemia.

Solid Tumors latency

Average latency = 20 years or more.

Specific examples of Solid Tumors

Lung cancer - relative risk of up to 8:1; Breast cancer - relative risk from 2.5 to 10.

Overall Quantitative Radiation-Induced Cancer risks

A single exposure to a lot of radiation (10 rads) doesn't result in as much excess mortality as does continuous exposure to low doses (1 rad, or 100 mrads).

Overall lifetime cancer risk increase

About 1% for every 10 rad (33% natural incidence).

Females radiosensitivity

About 70% more radiosensitive to cancer than males.

Newborns radiosensitivity

3 times more radiosensitive for cancer than a 25 year old.

70 year olds radiosensitivity

About 3 times less radiosensitive than a 25 year old.

Genetic Mutations Data from drosophila

Linear non-threshold curves, no 'dose rate' effect according to fruit fly data.

Doubling dose from 5 to 150 rads

Natural mutation rate is doubled in as little as 5 rads.

Doubling dose in Mega-mouse experiments

Much higher in mice than fruit flies, more like 100 or 200.

Substantial dose rate effect in Mega-mouse experiments

Same dose administered over a period of time results in fewer mutations than an acute exposure.

Chronic irradiation effect

Considerably less effective in inducing mutations in spermatogonia and oocytes.

Radiosensitivity of spermatogonia

More radiosensitive because they can't heal as fast as oocytes.

Frequency of radiation induced genetic mutations

Very low.

Pertinent conclusions from Mega-mouse experiments

Most mutations are harmful; any dose of radiation entails some genetic risk.

Proportionality of mutations to dose

Number of mutations are proportional to dose.

Linear extrapolation from high dose

Is a valid estimate of low-dose effects.

Increase in mutation rate from 1.0 rem

A dose of 1.0 rem per generation increases the natural spontaneous mutation rate by approximately 1%.

Fetal Effects

1st trimester is the most sensitive.

Risk of leukemia during pregnancy

Extends to the 2nd trimester.

Fetal exposure first two weeks high dose

Results in resorption of embryo or spontaneous abortion & death

Fetal exposure first two weeks low dose

Increased normal incidence of spontaneous abortion by only 0.1%

Normal incidence of spontaneous abortion

About 25 to 50%

Fetal exposure 2nd to 10th week

Period of major organogenesis

High radiation dose during organogenesis

Temporary growth retardation

Early in the organogenesis period

Severe skeletal anomalies

Later in the organogenesis period

Congenital abnormalities