Most people know that radiation is potentially harmful to living systems, unfortunately there are a number of misconceptions about radiation biology which are perpetuated in popular culture.
Radiation Biology History
1895-Roentgen announces discovery of X-rays
1896-(4 months later) Reports of skin effects in x-ray researchers
1902-First cases of radiation induced skin cancer reported
1906-Pattern for differential radiosensitivity of tissues was discovered.
Relative Radiosensitivity of Tissue
The relative radiosensitivity (sensitivity to radiation exposure) of a variety of tissue is shown in Figure 2-1 below:
Figure 2-1: Increasing Sensitivity to Radiation
Alan Jackson, 2001 from Seibert, 1996.
By 1906 Bergonie and Tribondeau realized that cells were most sensitive to radiation when they are:
Radiation sensitivityAuthor Note: When DNA, which had not been discovered at this time, has no backup (single strand).
- Rapidly dividing
- Undifferentiated
- Have a long mitotic future
Radiosensitivity is a function of the cell cycle with late S phase being the most radioresistant and G1, G2, and especially mitosis being more radiosensitive.
Mechanisms of Radiation Injury
Radiation can directly interact with a molecule and damage it directly. Because of the abundance of water in the body, radiation is more likely to interact with water. When radiation interacts with water, it produces labile chemical species (free radicals) such as hydronium (H.) and hydroyxls (.OH). Free radicals can produce compounds such as hydrogen peroxide (H2O2) which subsequently exert chemical toxicity. The body has sophisticated protections against this type of chemical damage. For example, this is why hydrogen peroxide foams when it is poured on a cut. The hydrogen peroxide is being destroyed by an extremely rapid enzyme, hydrogen peroxidase.
Nonetheless, while DNA and other repair methods are extremely capable of protecting the body, some fraction of the damage is not repaired or may be repaired incorrectly. In either case, if the DNA is damaged, several things can happen. The most likely is that the damage will be repaired before the end of the cell’s growth cycle. If not, the cell will probably die. There is some chance that the cell will survive and behave differently because of the damaged DNA.
Radiation Damage to DNA
Radiation-induced structural changes to DNA can be readily observed (Figure 2-2).
Figure 2.2: Radiation-Induced DNA Damage
Photomicrograph showing examples of radiation-induced chromosome damage in cancer cells following radiotherapy treatment (Bushong 1980). Courtesy of Scott Sorenson.
When DNA is damaged, the harm can be magnified by the cellular machinery. One example of a possible consequence is a cell which loses control over replication-this mutation is better known as cancer. Ionizing radiation is thought to initiate (start), but not promote (help grow) mutations.
Types of Radiation Effects
Acute Effects: Short term effects
Very large radiation exposures can kill humans. The lethal dose(LD) for half the population (50%) within 60 days is termed the LD50/60d. The LD50/60d in humans from acute, whole body radiation exposure is approximately 400 to 500 rads (4-5 Gy). The temperature elevation in tissue caused by the energy imparted is much less than 1° C. The severe biological response is due to ionizing nature of X-ray radiation, causing the removal of electrons, and therby chemical changes in molecular structures.
Deterministic Radiation Effects
A number of ionizing radiation effects occur at high doses. These all seem to appear only above a threshold dose. While the threshold may vary from one person to another, these effects can be eliminated by keeping doses below 100 rad. The severity of these effects increases with increasing dose above the threshold. These so-called deterministic (non-stochastic) effects are usually divided into tissue-specific local changes and whole body effects, which lead to acute radiation syndrome (Table 2-
Acute Whole Body Radiation Effects
Table 2-1: Acute Radiation Syndrome Sorenson, 2000
| Syndrome | Symptoms | Dose (rad) |
| Radiation sickness | Nausea, vomiting | > 100 rad |
| Hemopoietic | Significant disruption of ability to produce blood products) | > 250 rad |
| LD50/60d | Death in half the population | > 250 - 450 rad |
| GI | Failure of GI tract lining, loss of fluids, infections | > 500 rad |
| CNS | Brain death | > 2,000 rad |
Several factors, such as total dose, dose rate, fractionation scheme, volume of irradiated tissue and radiation sensitivity all affect a given organ’s response to radiation. Radiation is more effective at causing damage when the dose is higher and delivered over a short period of time. Fractionating the dose (i.e. spreading the dose out over time) reduces the total damage since it allows the body time for repair. Patient exposures are higher than attending staff but they occur over short periods of time whereas staff exposures are normally low and occur over several years.
Acute Localized Radiation Effects
The Table 2-2 provides examples of possible radiation effects to skin caused by typical fluoroscopy exposures. Note that patient and technique factors can substantially increase exposure rates, significantly reducing the time necessary for the subsequent effect.
Table 2-2: Dose and Time to Initiate Localized Radiation Effects
Please note these localized effects will not be seen immediately (in the clinic). These effects take time to develop and the minor effects may not be noticed and are often attributed to other causes. This effectively results in a lack of warning for serious effects such as dermal necrosis. This lack of warning has led the FDA, HFH Radiation Safety Committee, and HFH Hospital Medical Executive Committee (HMEC) to have concerns about fluoroscopy utilization. Consequently, fluoroscopy safety training and monitoring of fluoroscopy times were mandated.
Chronic Radiation Effects
Cataractogenesis
Cataract induction is of special interest to fluoroscopy operators since the lens of eye often receives the most significant levels of radiation (provided lead aprons are used). Radiation is known to induce cataracts in humans from single dose of 200 rad. Higher total exposures can be tolerated when accumulated over time. Personnel exposed to the maximum levels each year in the State of Michigan should accumulate no more than 150 rem to the lens of the eye over 30 years. As such, the risk for cataracts is likely to be small. Nonetheless, it is imperative that individuals who approach the State of Michigan dose limit (1,250 mrem per quarter) wear leaded eyewear which can reduce the radiation dose to the eye by 85%. Leaded eyewear will be provided, by Henry Ford Health System, to individuals with high eye doses. Once leaded eyewear is issued, this must be worn for all tableside X-ray procedures.
Stochastic (Probabilistic) Effects
Since the discovery of radiation by Roentgen, there have been many groups in which radiation effects have been studied (Bushong 1980) (Table 2-3):
Table 2-3: Groups Studied for Radiation Effects Scott Sorenson, 2000.
| Groups Studied for Health Effects |
| American Radiologists |
| Nuclear weapon survivors |
| Radiation-accident victims |
| Radiation-accident victims |
| Marshall Islanders (Atomic bomb fallout) |
| Residents with high levels of environmental radiation |
| Uranium miners |
| Radium watch-dial painters |
| Radioiodine patients |
| Ankylosing spondylitis patients (radiation therapy) |
| Thorotrast patients (radioactive contrast material) |
| Diagnostic irradiation in-utero |
| Cyclotron workers |
These experiments have repeatedly shown that exposure to large radiation doses results in an elevated risk of cancer. Thus, radiation is considered a known human carcinogen. The experimental data suggest a non threshold dose response relationship (Figure 2-3).
Figure 2-3: Stochastic Radiation Effects Courtesy of Alan Jackson, 2001
Extrapolation of effects at higher doses using a straight line, predict that very small radiation doses have corresponding small risk of causing a cancer. This straight line assumption, called the linear, no threshold, dose response relationship (LNT), involves the least amount of mathematical assumptions and is thereby consistent with the ancient principle of scientific philosophy known as Okam's razor (the simplest explanation which describes a phenomenon is the best). There are also some reasonable models which predict this relationship. The slope of this straight line can be used as a risk coefficient to compare radiation risks with other hazards.
The LNT hypothesis implies that any amount of radiation exposure will increase an individual's risk of cancer. Thus, all radiation doses should be mimimized or kept As Low As Reasonably Achievable (ALARA).
Due to statistical considerations, such as the normal incidence of cancer (~30%), the ineffectiveness of the production of cancer by radiation, stochastic effects can only be shown at doses much higher than that received by occupational workers. The effects from lower radiation exposures (such as those encountered occupationally) are extrapolated from observations made at high doses (Upton 1999). In any case, this linear assumption is expected to provide the most conservative, or highest, risk estimates. The slope of the line is the risk coefficient.
Radiation Risk
The cancer risk coefficient derived from the LNT model for radiation exposure is approximately 4.8 * 10-4 per rem. To put this number into perspective, imagine that you have two similar groups of 10,000 people; exposed and not exposed. Each member of the exposed group receive 1 rem 1,000 mrem) of radiation exposure. The control group does not recieve any additional radiation exposure beyond that received by natural sources. Since the natural incidence of cancer is about 30%, the control group would expect about 3000 people to die from cancer. In comparison, the exposed group would expect that about 3005 people would die from cancer. Thus, the exposed group should expect about 5 additional cancers from the 1 rem exposure.
One way better understand radiation risks is to compare radiation risks with other commonly accepted risks (Figures 2-4 and 2-5).
Figure 2-4: One in Million Risks Alan Jackson, 2001
Figure 2-5: One in Million Risks Alan Jackson, 2001
Radiation Induced Genetic Damage
Since radiation causes damage to DNA, genetic effects in human populations have long been suspected. Unrepaired or incorrectly repaired chromosonal damage can be passed on to subsequent generations. To date, there have been no studies which show an increase in genetic disorders in human populations. Nonetheless, animal studies have shown a relationship between radiation exposure and genetic defects which suggest a linear, no threshold, dose response relationship (LNT) much like that seen with cancer.
The 7 million mice, "Megamouse" project revealed the following conclusions (Lam 1992):
- Different mutations differ significantly in the rate at which they are produced by a given dose.
- There is a substantial dose rate effect with no threshold for mutation production.
- The male was more radiosensitive than the female. The males carried most of the radiation induced genetic burden.
- The genetic consequences of a radiation dose can be
greatly reduced by extending the time interval between
irradiation and conception. Six months to a year is
recommended. - The amount of radiation required to double the natural and spontaneous mutation rate is between 20 to 200 rads.
Radiation Induced Premature Aging
In animal populations, radiation was correlated with premature aging .
In-utero Radiation Health Effects
Once conception has occurred (mother is pregnant), the unborn child (fetus) can be harmed by radiation. Certainly, the unborn child can have the same health problems that an adult might have such as cancer and genetic defects. The Law of Bergonie and Tribondeau predicts that a fetus would be exquisitely sensitive to radiation since they are:
1. Rapidly dividing;
2. Undifferentiated; and
3. Have a long mitotic future.
Studies of children exposed to x-rays in-utero support that prediction. Thus, based on a concern for cancer induction, X-ray examination of pregnant patients has transformed from a standard health screening study to an extremely rare study. Nonetheless, some X-rays of pregnant patients, particularly those to protect the life of the mother, are performed when necessary to protect the life of the mother typically under the guidance of a Radiologist.
In addition to the health effects which are a concern for an adult, there is also a serious concern about the possibility of developmental errors (teratogenesis) which can occur. There are three general prenatal effects which have been observed:
- Lethality;
- Congenital abnormalities at birth; and
- Delayed effects, not visible at birth, but manifested later in life.
Figure 2-6: Fetal Developmental Radiation Risks
Courtesy of Scott Sorenson, 2000
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