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79 Cards in this Set
- Front
- Back
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Tissue Response
Acute Effects Late Effects |
Effects on whole body
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Tissue Radiation Response =
There are many differing cell types within the human body, |
the differing cell types have associated radiosensitivities.
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Law of Bergonie & Tribondeau
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Ionizing Radiation is more effective against cells that are actively mitotic, undifferentiated (un-specialized), divide rapidly and have long dividing future. This is one of the most important concepts of Radiobiology
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Differentiated Cells
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Cells which have a specific function in the body, e.g. pancreatic cells which produce insulin, thyroid cells produce thyroid hormone.
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Undifferentiated cells
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cells which are precursor cells to cells with a more desired function. Stem cells are undifferentiated. De-population of this cell group is dangerous to the life of the organism.
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LymphTocytes are the one
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exception to the law of B&T. They rarely divide and die in are interphase, yet they VERY sensitive to radiation. Sensitive cells normally die during mitosis.
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Cell Population and Radiosensitivity - 4 categories
1. Vegetative Intermitotic Cells (VIM) |
Rapidly dividing, undifferentiated cells that have short lifetime. High radio sensitivity; example= type A spermatagonia, basal cells of the epidermis, intestinal crpt cells
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2. Differentiating Inter-mitotic Cells (DIM)
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Actively dividing, but more differentiated than VIM cells. Ex. type B spermatagonia (on it's way of becoming an adult sperm), myelocytes
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3. Reverting Post Mitotic Cells (RPM)
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Normally not proliferating, but can retain reproductive integrity. Radio-resistance population. Ex. Liver cells, glandular cells and mature lymphocytes. LYMPHOCYTES ARE THE EXCEPTION. They are part of this group but are radiosensitive
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4. Fixed Post Mitotic Cells (FPM)
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No division, highly differentiated in form and function. Can beshort lived or long lived. Most radio-resistant. Ex. nerve cells, muscle tissue, red blood cells.
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Going from # 1 to #4
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We move from high radio-sensitivity to lower radio sensitivity
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We can also categorize these the types of cells in tissues and organs which have two compartments
1. The parenchymal compartment |
Containing the cells typical of that organ which carry out the unique functions of a particular tissue.
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2. The stromal compartment
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Composed of connective tissue and blood vessels
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The parenchymal compartment can be composed of
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one or more categories of cells.
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Prodromal Syndrome
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Signs and symptoms shortly after a significant radiation exposure but can occur up to 6 days later. There seems to be a threshold of 50 to 100 rads for the appearance of any symptoms.
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Prodromal Syndrome 2
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High exposures ( few thousand rads) symptoms occur within 5 to 15 minutes. Symptoms can persist for days.
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Prodromal Syndrome 3
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Severe response usually indicates a poor clinical prognosis.
Symptoms fall into 2 categories, neuromusclar and gastrointestinal. |
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Latent Period then you can experience:
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1. Hematopoietic sydrome = kills WBC, 400 rads
2. GI Syndrome = 1,000 rads 3. Cerebrovascular = 10,000 rads |
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Neuromusclar ( Signs and Symptoms can be expected at about LD50)
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Fatigue, vomiting
Additional signs to be expected at a lethal dose or higher Fever, hypotension |
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Gastrointestinal (Signs & Symptoms can be expected at about LD50)
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Anorexia
Additional Signs and Symptoms at a lethal dose or higher Immediate Diarrhea |
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The first prodromal syndrome show up after
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6 hours
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Latent Period
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Following the Prodromal Syndrome, there is normally a latent period where there are no symptoms. The length of the latent period depends on the total dose received. With a higher dose, the latent period is shorter.
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Hematopoietic Sydrome
30 day latent period = In 30 days, all WBC will die |
Total body dose of 300-800 rads. Sufficient to sterilize actively dividing precursor cells of RBS's platelets and WBC's. LD 50/60 for humans is about 325 rads.
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Problem
- SEE P.P |
Doses of radiation are commonly related to a number of Chest X rays by media. If a typical chest X ray is about 12 mrads, about how many CHest X rays would be required for a lethal dose?
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Gastrointestinal Syndrome
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Total body dose of 1000 rads or more. No record of anyone surviving a dose of this order.
Nausea, vomiting, prolonged diarrhea, loss of appetite, weight loss, death occurs with 5 - 10 days. |
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Gastrointestinal Syndrome 2
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Mostly caused by depopulation of the epithelial lining of the gastointestinal tract and intestinal crypt cells. Population will not recover. Ex. A self renewing, stem cell population in the VIM category.
Several death syndromes occurred like this at Chernobyl |
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Cerebrovascular Syndrome
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Total body dose of about 10,000 rads or 100 gy. Death occurs in a matter of hours.
Severe nausea, and vomiting, disorientation, loss of coordination, respiratory distress, diarrhea, seizures, coma, death. |
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Cerebrovascular Syndrome 2
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Not completely understood. All organ systems are affected, however, it is most likely the affect on the nervous system which leads to death. Only a few people have eve received enough radiation exposure to have the cerebrovascular syndrome.
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Humans develop symptoms and recover more slowly than any other mammal.
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Peak incidence of death occurs at about 30 days but continues for up to 60 days. Transfusions are usually not given because it delays regeneration of bone marrow.
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Begins with prodromal syndrome followed by a symptom-less latent period. At about 3 weeks.....
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bleeding can occur from a platelet depression, epilation, impairment of immune system. Anemia from RBC depression does not usually occur. Infection is usually the cause of death if not controlled.
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Treatment for persons exposed to this dosage....
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of radiation is isolation and antibiotics to prevent infection.
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Bone Marrow transplants are of questionable use as treatments. There is a small window of
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about 800-1000 rads opportunity were they may be effective. To compound this problem, there is difficulty in matching bone marrow type.
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See example in P.P
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13 victims of the Chernobyl Reactor......... etc
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Radiation Carcinogenesis
Cancer is a late effect of radiation on somatic cells of the body. |
Late effects are known as non-threshold or stochastic effects. They are caused by cells which survive exposure to radiation.
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Radiation Carcinogenesis 2
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The implication for non-threshold effects is that even very small amounts carry some risk. Therefore, no amount of radiation is completely safe.In theory, a single photon is all that is required to produce a malignant change in the cell.
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In contrast to stochastic effects, deterministic or non-stochastic effects have
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a zero chance of occurrence below a certain threshold. Deterministic effects have a threshold dose. The severity of the effect increases with dose above threshold.
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Our date on the induction of cancer by radiation comes from specific groups who
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were either accidently or intentionally exposed to radiation.
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1. Early X- Ray workers, physicists, engineers. Skin cancer
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2. Pitchblend and uranium miners
Lung Cancer |
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3. Radium clock dial painters
Bone Caner |
4. Patients given X-Ray therapy for ankylosing spondylitis and tinea capitis (Grenz Ray Treatment)
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5. Patients given Thorotrast contrast medium ( liver cancer)
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Radium = heavy element + alpha emitter + hang out in bones, once inside the body, very dangerous
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6. Patients given multiple fluoroscopies for TB
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7. Japanese A-bomb survivors
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8. Patients injected with radium salts for treatment of TB or ankylosing spondylitis which is a
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degenerate condition of the vertebral bodies, thought to be an autoimmune disease.
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Oncologic Terminology
Carcinoma |
Arising from epithelial tissue, tissue lining internal or external organs, glandular tissue
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Sarcoma
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Arising from connective tissue, muscle bone or fat, bone vascular tissue
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Lymphoma
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Arising from lymphatic tissues or white blod cells, leukemia
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Additional terms to describe cancer exist that help to specify the cell type. For instance,
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an adenocarcinoma arises from glandular epithelium. Adeno = gland, carcinoma = epithelial tissue
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How do cancer cells differ from normal cells??
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They don't stop reproducing. Normal body cells are programmed to die after about 50-60 divisions
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Cancer cells are
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immortalization = they don't die
- They don't obey the signals from neighboring cells, loss of contact inhibition |
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How do cancer cells differ from normal cells?? 2
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Cancer cells do not stick together. The ability to metastasizes which means spreading and usually kills the person
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How do cancer cells differ from normal cells?? 3
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Cancer cells do not become specialized, unlike normal cells, they do not keep maturing. With more and more divisions they become more primitive and reproduce more haphazardly.
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Cancer cells differ in their levels of organization and
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differentiation. All cells of a tumor ma share some feature of the tissue from which they originated. However, an ANAPLASTIC tumor is a tumor with little or no evidence of differentiation. Poor prognosis diagnostic
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The level of differentiation is determined by
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histopathological examination in the laboratory using a prepared sample of the cancerous tissue obtained from a biopsy. The biopsy tissue is given a grade according to this assessment.
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Grading System
GX G1 G2 G3 G4 |
grade cannot be assessed
well differentiated moderately differentiated poor differentiation Undifferentiated |
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From Better to
Worse |
Cancers are further identified by the size of the primary tumor, the involvement of lymph nodes and the level of metastasis.
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Metastasis
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The ability of a cancer to spread to other arts of the body where new tumors grow. This is the most important property of cancer which leads to the death of an hosts.
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Carcinogen
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A cancer causing agent. Can be chemical,viral, ionizing radiation or non ionizing radiation (UV)
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Latent Period of Cancers
Solid Tumors = 15 years latent period |
The amount of time between exposure to radiation & development of the health effect. Varies for type of cancer. Solid Tumors have longer latent periods than leukemia's. Leukemias tend to appear earliest after irradiation at about 7 to 12 years.
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More recent data has shown that there is not a definite latent period.
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Regardless of when persons are exposed to radiation, the increase in cancer occurs later in life, around the time when spontaneous cancer occurs. This suggests a complex process of cancer development.
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Risk
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Models to access risk are necessary when it comes to radiation exposure because
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1. Data obtained at relatively high doses must be
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extrapolated to the lose doses which the public is more frequently exposed to.
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2. No large groups of persons exposed to a
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significantly large amounts of radiation have been followed for their entire lifespan
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3. The greatest and best data for an exposed population comes from the Japanese A bomb survivors;
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The data from this population must be applied to different populations which may be very different. Before hand, Japanese had/lived a very healthy lifestyle.
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Absolute Risk Model
- Crops of age periods which susceptible of the age group 40-50 |
Attempts to measure the cases of cancer which are additional to the normal incidence in the population over a defined period of time. Measured in cases/million people/rad/
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Relative Risk Model
- Risk increases as you age! |
Attempts to measure the increased incidence at all ages following radiation exposure. Indicates there is an increased risk throughout a person lifetime following exposure, there will be more cancers in older persons.
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Radiation is known to cause an
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increase in the incidence of leukemia, breast cancer, thyroid cancer, lung cancer, bone cancer and skin cancer.
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The lung, breast,
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and thyroid are especially sensitive tissues.
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The current most accepted model for cancer risk from radiation exposure is a
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time- dependent relative risk model.
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Factors Affecting the level of risk include:
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-the dose
-the square of the the dose the persons age at exposure -the time since the exposure -type of cancer |
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Factors Affecting the level of risk include:
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-type of radiation
-presence of factors such as exposure to other carcinogens or exposure to promoters that may interact with radiation |
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Linear vs. Linear Quadratic Risk Model
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The linear model indicated that the risk of cancer is proportional to dose at all doses. Risk per rad is the same for all doses.
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Linear Quadratic Risk Model
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Indicates that at low doses, the risk is less with risk increasing at higher doses.
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Different cancers seem to follow different risk models:
Linear Model = |
breast,thyroid
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Linear Quadratic Model
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bone, leukemia
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Charts
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Look at P.P
- Linear goes through the origin |
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The induction of cancer studies by radiation are based primarily on
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subjects exposed to acute, high doses of radiation.
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The BEIR V (government report) acknowledges that there is a
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dose-rate effect; that there are fewer malignancies of the dose is delivered over time
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Chart page 15
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Long term radiation risk factors are more difficult to asses. The predictions are based on the use of risk models.
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Linear Model
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The model used for techs, because it is a more specific model
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Chart 2 page 15
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In particular for low LET exposure linear and quadratic dose-response models differ considerably in their risk assessment.
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