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60 Cards in this Set

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Which incidents are more important: Lethal Acute dose effects or long term effects?
Long term effects
What are the characteristics of Late effects?
1. They are manifested after long periods of time after the exposure.

2. They may remain dormant for many years.

3. They may show up in succeeding generations.
Three factors.
What are the two categories of late effects?
1. Somatic effects (seen in the individual).

2. Genetic effects (seen in future generations).
Two general types.
What type of exposures cause Late effects?
1. Individuals who survive acute high doses.

2. Exposure to a single low dose.

3. Chronic low dose exposure
Give examples of Chronic Low dose exposures.
1. Patients receiving radiologic/nuclear medicine procedures.

2. Occupationally exposed persons.

In this group of individuals these effects are even more insidious because there are no acute effects that mark them for future study.
How do late effects differ from other types of injury?
Other effects are a result of cell, tissue or organ death.

Late Effects arise in those cells which survive the initial exposure but nonetheless retain some memory of it.
Interms of probability and severity how can Late effects be categorized?
1. Nonstochastic or Deterministic.

2. Stochastic effects.
Two ways
How are Nonstochastic (deterministic) effects defined?
1. A deterministic effect has a Threshold Dose.

2. The severity of the effect is also dose related.
Two ways.

Consider how dose is related.
How are Stochastic effects defined?
1. These are effects that do not exhibit a threshold.

2. Any dose, no matter how small, carries a probability of inducing the effect.

3. Increase the dose and you increase the probability.

4. The severity of the effect will not increase with dose.
4 ways.

Is threshold important?

What about probability?

What about severity?
What is the single most important late somatic effect induced by radiation?
Carcinogenesis

Particularly after low doses.
Is it easy to determine the degree of risk of developing cancer after radiation?

Why?
NO!

This is because the time between the exposure and the appearance of cancer is very long.
What is the characteristic of incidence risk in Leukemia?
Leukemia risk increases to a peak between 7 and 12 years. And essentially returns to the control incidence by 20 years post exposure.
Consider the shape of the curve.
What is the Latent period for solid tumors?
It can vary between 20 and 30 years.

The mean latent time for all radiation induced cancers is about 25 years. (except Leukemia)
Other than probability, what else is important to know about Risk?
It is also critical to know if the individual continues to be at risk throughout life.
Does the risk cease or continue through life?
What is Absolute Risk?
The risk iappears to be a discrete event.

The risk rises for a given period of time then returns to the natural incidence of the disease
Consider the incidence curve for leukemia.
What is Relative Risk?
An individual may be at risk throughout his or her lifetime.
Why is it difficult to establish what cancers carry an absolute versus relative risk?
1. To obtain much of this data an exposed population would need to be followed and studied until all its members have died.

2. This has not been done yet in humans.
How is the risk of cancer induction after low dose exposures determined?
This is estimated by extrapolating the data from the high dose models.
What models are used to determine Risk?
1. The Linear model.

2. The Linear Quadratic model.
Two methods.
How do the models differ?
1. The linear model assumes the risk per rad is the same at high and low doses, the incidence of cancer follows a straight line.

2. The linear quadratic model assumes smaller risk per rad at low doses. Incidence is a concave curve upward.
What are the disadvantages of the different Risk models?
1. A linear extrapolation might overestimate the real risk in the low dose range and underestimate it in the high range.

2. An extrapolation of the linear quadratic model does the reverse.
Think of the Linear and LinearQuadratic curves overlaid.
Which model do radiobiologists prefer?
The linear quadratic model.
What is an etiologic factor?
A causative factor.
How are Incidence rates for cancer determined?
By comparing the expected incidence in a population to the incidence in an exposed population.
How is the Excess Risk defined?
Number of excess cases per 1 million exposed people per year per rem.
What problems arise with the statistical nature of these studies.
1. Huge variances in the populations studied (climate, nutrition, social, economic etc.

2. Studies of this type are unable to exclude other factors that might play a part in the risk increase.

3. Very important is the fact that the dosimetry in most cases is only estimated.
Why does the incidence of leukemia increase at low doses but diminish at high ones?
After low doses the cells are not killed, but survive only to undergo malignant transformations later on.

After high doses, the cells do not get an opportunity to express malignant change because the they are killed by the dose.
What are the sources of data for radiation induced cancers in humans?
1. Occupational exposure

2. Atomic bomb survivors

3. Medical exposure

4. Fallout accidents in the pacific test grounds
Four items.
What type of malignancies are implicated with radiation?
leukemia
skin carcinoma
osteosarcoma
lung, thyroid and breast cancers.
sar·co·ma (sahr-ko'm ) [ sarc- + -oma ]
any of a group of tumors usually arising from connective tissue, although the term now includes some of epithelial origin; most are malignant.
What modes of radiation has Leukemia been linked to?
1. The early days of radiation discovery.

2. Atomic bomb survivors.

3. Patients treated for ankylosing spondylitis.
Three items.
Does radiation increase the risk of all Leukemias?
No.

Acute and Chronic myeloid in irradiated adults.
Acute lymphatic in exposed children.

Chronic lymphatic does not appear to be influenced by radiation exposure.
What were the increased incidences of Leukemia at Hiroshima and Nagasaki?
In Hiroshima the increased incidence was fivefold.

In Nagasaki, the increased incidence was threefold
What explained the differences of increased incidences of Leukemia at Hiroshima and Nagasaki?
At Hiroshima, half the dose was x-ray and half neutrons (heavy particle damge).

At Nagasaki, 90% of the dose was x-ray.
What was the increase in leukemia incidence in persons treated for Ankylosing Spondylitis?
Over 100% was seen at the higher doses.
15000 patients were treated for this painful disease using radiation. (1-20Gy) in Great Britain between 1935 to 1944. .
What two problems were evident with the dosimetry in the Ankylosing Spondylitis studies?
1. The population was initially ill, and consisted of primarily males. (this could have overestimated the risk).

2. An appropriate control group,(same disease but not treated with radiation did not exist)
Consider who was treated and also whether the Scientific method was used.
Is the incidence of leukemia in radiologists higher than in the general population?
No.
Early studies on American doctors had shown an increased risk in this field.

However studies done outside the country revealed that this might not be the case.
In which group of people was Skin Carcinoma first seen?

Why?
Many technicians and radiologists reported reactions soon after Roentgen discovered x-rays.

The early x-ray machines were of low energy with little filtration, exposures were readily absorbed in the superficial layers of the skin.
What other source of data is there for Skin Carcinoma?
Individuals treated for acne and ringworm.
When were incidences of Osteosarcoma first seen?

Why?
Watch dial painters (1915 – 1930).

Pointed their brushes using their lips.

Radium was used in the paint to illuminate the dial of the watch.

Radium is a bone seeker, that is not excreted, so doses accumulate in the skeleton.

Radium liberates alpha particles, which have an RBE nearly 20 times that of x-rays.
When were incidences of Lung Carcinoma first seen?

Why?
Pitchblende miners in Germany and uranium miners in the western United States.

Radon gas. An alpha emitter inhaled directly into the lungs.
When were incidences of Thyroid Carcinoma first seen?

Why?

What increase?
The irradiation of the thymus in infants to reduce thymic enlargement in the early 1930’s.



A hundred fold increase.
Doses in these infants ranged from 1.2Gy to a staggering 60Gy (6000rad).
What other incidences of Thyroid Carcinoma were next seen?
Children in the fallout zones of the Marshall islands and Hiroshima and Nagasaki have shown increases as well.
What is the latent period for radiation induced Thyroid Carcinoma?
The latent period for this radiation induced cancer appears to be 10 to 20 years.
Have studies shown conclusively that radiation increases the incidence of Breast Carcinoma?
Yes.
Does incidence of Breast Carcinoma follow a Linear or Linear Quadratic model?
Linear
When were incidences of Breast Carcinoma first seen?
1. Female survivors of the atomic bomb attacks.

2. Canadian women with tuberculosis were subjected to multiple fluoroscopies.

3. Women treated for benign breast disease.
In which other cancers has radiation been implicated
1. Salivary gland and some sarcomas.
Any of a group of tumors usually arising from connective tissue, although the term now includes some of epithelial origin; most are malignant.
What is the increased risk for In Utero exposure?
Because of the sensitivity of the developing embryo and fetus it is suggested that a value of 1.5 to 2 be used to estimate the increased risk of inducing malignancy after fetal irradiation.
How Does Radiation Induce Cancer?
1. Structural changes in chromosomes resulting in mutations are a known effect of radiation.

2. The current hypothesis is that radiation, through the translocation of genetic material, allows oncogenes normally unexpressed to be expressed, ultimately causing cancer.
Two possible ways.
What is an Oncogene?
Oncogenes are genes whose expression is speculatively linked to the conversion of normal cells to cancer cells.
What is the lowest dose implicated for malignancies in adults?
.25 Gy

Lower for In Utero exposures.
What is the range of Latency periods for the different types of radiation induced cancers?
5 to 30 years.
Is the incidence of radiation induced cancer decreasing?

Why?
Yes.

1. The knowledge of these dangerous effects has led to strict regulations regarding radiation usage and a lowering of the MPDs to occupationally exposed personnel and the general population.

2. The cessation of the misuse of radiation as a panacea for treating illnesses of all types.
Define:

Spontaneous mutations.

Mutation frequency.
Naturally occurring changes that take place in DNA and genes.

A certain number of spontaneous mutations arise in each generation.
They are permanent and heritable
What can alter the frequency of spontaneous mutations?
Viruses,chemicals, and radiation.
They are called MUTAGENS.
What is the unit of measurement for the determination of radiation effect on mutation frequency?
The doubling dose.

Defined as that dose of radiation which ultimately doubles the number of spontaneous mutations.
Does radiation produce new mutations?
Radiation produces no new mutations, it only increases the already existing number observed.
What conclusions could be drawn from Animal Data?
1. All mutations did not show the same susceptibility to induction by radiation.

2. Males were found to be more sensitive than females.

3. The effects can be reduced by allowing a time period to elapse between exposure and conception. (6 months in humans).
This indicates that the doubling dose is not constant for all mutations.

The burden of genetic effects in the population is carried by males.

The cells have time to repair
What conclusions could be drawn about Mutation?
1. Radiation simply increases the incidence of the same mutations that occur spontaneously.

2. It produces no new mutations.

3. The incidence of radiation induced mutations follows a linear relationship with dose.

4. The incidence of mutations is most likely dose-rate dependent in humans.
Four factors.

The speed at which the dose is given. There is more risk of damage at higher rates
What other conclusions can be drawn about mutation?
1. Mouse data is probably not to far off from what would be relevant to humans.

2. The doubling dose is the dose required to double the spontaneous mutation rate.

3. Based on atomic bomb survivors the general doubling dose is said to be 156rem (1.56sv).
It is estimated to be in the range of 50-250rem.

A & H-bomb number of 156 Rem is the best to use.