|Year : 2002 | Volume
| Issue : 1 | Page : 21-32
|A review of the current concepts of radiation measurement and its biological effects
SB Grover, J Kumar
Department of Radiology, Safdarjang Hospital, New Delhi-110029, India
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| Abstract|| |
Radiation measurement units have undergone a change from Rads and Rems to Grays and Sieverts. However, radiobiology literature uses both systems, resulting in confusion for Radiologists. Radiation exposure is quantified by the unit Kerma which is currently expressed in Grays and Sieverts. In this review, we attempt to explain both the earlier units and the present system of SI (System International) units. This review also appraises the reader that human beings live under significant doses of radiation from natural sources, such as the naturally occurring radioactive gas radon, besides that from man-made sources such as X-rays, radioactive medication and nuclear installations. The biological effects of radiation had been studied and documented within few years of the discovery of X-rays and further information has consequently been available from longitudinal studies on populations affected by the atomic bomb. Biological effects are classified as deterministic (or certainty effects) and stochastic effects. Both deterministic and stochastic effects may either result in changes in organs (somatic effects) or in the genes (genetic effects). Deterministic or certainty effects are directly related to a known dose of radiation and have a dose threshold and their severity is also dose related. Stochastic effects are random events which are not dose related but their probability increases with an increase in the radiation dose. Carcinogenesis and genetic mutations are stochastic effects. The radiosensitivity of organs varies, therefore the various doses at which the deterministic effects on different organs occur are reviewed. The doses likely to be associated with 'risks of cancer' are also enumerated and the doses related to genetic mutations are also discussed. The effects on the fetus are both somatic and genetic and the most radiosensitive period is 8-17 weeks of gestation. The safety of radiographic imaging is discussed with reference to doses delivered in common radiological studies. Radiation doses permissible during pregnancy in the general population and in radiation workers are also highlighted.
Keywords: Radiation units, kerma, gray, sievert, deterministic effects, stochastic effects
|How to cite this article:|
Grover S B, Kumar J. A review of the current concepts of radiation measurement and its biological effects. Indian J Radiol Imaging 2002;12:21-32
|How to cite this URL:|
Grover S B, Kumar J. A review of the current concepts of radiation measurement and its biological effects. Indian J Radiol Imaging [serial online] 2002 [cited 2020 Jun 5];12:21-32. Available from: http://www.ijri.org/text.asp?2002/12/1/21/28413
| Introduction|| |
Radiation measurement units have undergone a change from Rads and Rems to Grays and Sieverts. However, radiobiology literature uses both systems, resulting in confusion for Radiologists. Radiation exposure is quantified by the unit Kerma which is now expressed in Grays and Sieverts. In this review, we attempt to explain both the older and the new SI system (System Internationale). In sections on specific radiation doses causing the biological effects, we have presented the conversions in the SI system, in case these had been cited in the older units. In this review we inform that background radiation from natural sources also comprises significant radiation doses during a person's life span. We take the reader on a brief trip down the history of the initial case records of biological effects and the original reports which form the basis of our present day knowledge. The pathophysiology of biological effects of radiation, the deterministic effects on various organs and the possible doses related to stochastic effects are also reviewed. Effects on the fetus and safety of radiographic imaging during pregnancy are also enumerated.
Radiation definition and properties
Radiation is defined as energy in transit and comprises of electromagnetic rays (X-rays or gamma rays) and particulate radiation (electrons, protons, neutrons, alpha particles, negative pi-mesons, and heavily charged ions) . X Rays and gamma rays are identical except that they differ only in their source of origin. X Rays are produced mechanically by making electrons strike a target that cause the electrons to give up their energy as X rays,
whereas gamma rays are produced by nuclear disintegration of radioactive isotopes .
X Rays and gamma rays are packets of energy or photons and have no mass or charge. They travel in straight lines.
The wavelength of X-Rays is 10-10 metres which is = 1A0 (A0 = angstrom)
The wavelength, l of electromagnetic radiation is related to the frequency n by the formula :
ln = c (where c is the speed of light)
Wavelength being inversely proportional to frequency, can also be denoted as v = c/l
Each photon contains energy equal to hn,
or E = hv (where h is Planck's constant, Planck's constant = 6.634 x 10-34 )
Since ln = c and n = c/l ,
the energy of the Xrays can be calculated,
by replacing n in the equation E = hn
as E = hc/l. (1).
The difference between non- ionizing and ionizing radiation is the energy of the individual photons and is not dependent on the energy of the total dose of radiation.
Units of Radiation and Exposure
To discuss the biological effects of radiation, a concept of the units of radiation measurement is necessary.
The unit of radiation exposure is the Roentgen (R), defined as an amount of x-rays or gamma rays that produces a specific amount of ionization in a unit of air under standard temperature and pressure; this quantity can be measured directly in an air chamber : it is 2.58 x 10-4 C/Kg air .
Exposure is defined strictly for air as the interacting medium. To characterize an X-ray field, the quantity of exposure should be measured.
Exposure is quantified by the unit Kerma.
Kerma is an acronym for Kinetic energy released in material.
Kerma quantifies the amount of energy transferred to charged particles from ionizing photon radiation.
The unit of Kerma was the Rad and is now the Gray (Gy).
The unit for measurement of the amount of energy deposited in tissue is the 'rad' or radiation absorbed dose.
The unit rad is defined as the absorption of 0.01 joule of energy in one kg of material.
This unit is now replaced by Gray.
One Gray is the absorption of one joule per kg of tissue (i.e. one gray = 100 rads)
since 1 rad = 0.01 joule energy/Kg
and 1 Gray = 1 Joule per Kg
Therefore, 1 Gray = 100 rads (2).
For air, 1 Gy of Kerma is equivalent to 115R of exposure,
which has been rounded off to 1 cGy being approximately = 1 Roentgen .
When X-rays are absorbed in tissue, energy may break chemical bonds and thus cause damage to the cells that comprise the tissue. The biological effectiveness of a given absorbed dose of one type of ionizing radiation is not necessarily the same as that of an equally absorbed dose of another type of radiation. For this reason, a unit of radiation dose equivalent was developed which was called, rem, an acronym for roentgen equivalent man. It represents dose in rads multiplied by a quality factor, QF (also called relative biological effectiveness, RBE). The quality factor for the various types of radiation is as follows  :
The radiation dose equivalent for which the unit was rem, has now been replaced by 'Sievert' in the SI units (systeme internationale).
Seivert is defined as the dose in gray multiplied by the quality factor. The Sievert is currently used for devising radiation protection standards. (Sv = Gray x QF)
We have summarized below, a simple overview of the definitions and conversion of these units of radiation:
Roentgen = amount of radiation that produces a specific amount of ionization in a unit of air under standard temperature and pressure.
Kerma = Kinetic Energy transferred to charged particles in Rads / Grays.
Rad = radiation absorbed dose
= 100 ergs of energy / gm of tissue
= 0.01 joule of energy / kg of tissue
1 Gray = 100 Rads = 1 joule of energy / kg of tissue
1 Rad = 0.01 Gray
1cGy (centi Gray) = 1 Rad
1 mGy (milli Gray ) = 0.1 Rad
Rem = radiation equivalent man
= rad x RBE (QF) / (relative biological effectiveness or Quality factor)
Seivert = Gray x QF
1 Seivert = 100 rems
(1000 milliSv or mSv)
1 mSv = 0.1 rem ( for Xrays which have a qualifying factor of 1) = 1 mGy
The DS - 86 system
The radiation exposure by atomic bomb is currently measured by a dosimetry system devised in 1986, and is called the DS-86 system. This system follows the current units of Grays and Sieverts and is used for calculating the organ doses. DS-86 system takes into account the spectrum and amount of radiation released by the bombs, attenuation with distance and physical shielding, free in air Kerma reaching the person, body position with respect to atom bomb position, and also the further attenuation of the radiation reaching the gonads by the intervening body tissues .
Sources of Radiation
Human beings live in a sea of continuous radiation, which is both natural and man-made. The natural sources include cosmic radiation from space, radiation from the earth and its internal radionucleide. Artificial sources of radiation include X-ray equipment, nuclear weapons and radioactive medication .
Most of a person's lifetime radiation exposure is from low-dose background radiation. The average annual effective dose for persons in the United States is estimated to be about 3.6 mSv. About two-thirds of this radiation is from natural sources, of which radon, cosmic rays, radio-nuclides in the earth and radioactive elements in the body are the major contributors . Radon is believed to contribute about 55 percent of a person's total background radiation exposure. This represents about 2 mSv of exposure per year. Radon is a colorless, odorless and tasteless alpha particle emitting radioactive gas, which is derived from naturally occurring uranium deposits in the earth. Radon itself is not particularly harmful, but some of its alpha-emitting polonium radioactive decay products may heavily irradiate bronchial epithelium cells for many months or years .
Cosmic radiation accounts for about 0.3 mSv of background radiation per year at sea level. The earth's atmosphere acts as a shield, so that the dose is about doubled with every 1500-metres increase in altitude. Radioactive potassium and carbon and other radio-nuclides within the body contribute about another 0.4 mSv to the average person's annual background radiation exposure. Radioactive decay of thorium and uranium radio-nuclides in the earth's crust constitute the major sources of terrestrial radiation, which, in most areas, is about 0.3 mSv per year . The remaining 18 percent of a person's total background radiation exposure is from man-made sources. Diagnostic x-ray and nuclear medicine account for over 0.5 mSv of the estimated annual total of about 0.65 mSv .
Most acute or intermittent excessive exposures to ionizing radiation occur in association with radiation therapy, preparation for organ transplantation, nuclear weapon detonations, nuclear reactor accidents or accidental ingestion of radio-nuclides .
Since background radiation can never be minimized to zero level, our efforts are obviously targeted at reducing exposure from man made sources. Therefore, doses and effects of x-rays are of primary concern to the diagnostic radiologists.
Effects of radiation
The epoch making discovery of X-rays by Roentgen in November 1895, led to their almost global prolific use, utilising Crook's tube as an inexpensive agent. Within few months of Roentgen's discovery, eye complaints and severe progressive dermatitis were reported. In 1896, one of Edison's assistants Clarence E Dally, involved in the production of X-ray tubes, who had been using his own hand to test their output, developed ulcerating carcinoma of his repeatedly exposed left hand. Delayed effects of radiation began to be documented only 20 years after their initial discovery, through individual case reports. The death of Professor Benjamin Brown in 1911 was also attributed to X-ray exposure causing visceral degeneration, as a result of his earlier experiments, of fluoroscoping his own abdomen continuously for a 2 hour period during 1896. Germ line mutation as a delayed effect of ionizing radiation was documented by Muller in 1927 and won him the Nobel prize. In 1928, Murphy reported 14 cases of microcephaly and mental retardation in children of mothers who had received pelvic radiotherapy early in pregnancy. The 1929, Murphy and Goldstein documented 16 more patients with similar defects of microcephaly and mental retardation among children whose mothers had received pelvic radiotherapy early in pregnancy. In 1936, Percy Brown a Radiologist historian, recorded case histories of adverse effects of radiation which occurred in people exposed from 1911 onwards. In 1942, Dunlap reported radiation induced leukemia in Radiologists and other radiation workers .
In 1947, the Atom Bomb Casualty Commission (ABCC) was established to undertake scientifically designed studies in Hiroshima and Nagasaki, to establish the radiation effects following the atomic bomb blasts in these two cities. This commission reported the incidence of genetic effects, mutations, cataracts, leukemias and other malignancies in the population exposed in these blasts. These studies also documented effects on unborn fetuses, including microcephaly and mental retardation. In 1956, Stewart et al reported increased frequency of leukemia in children with history of radiation exposure during fetal life. In 1975, the ABCC was reorganized and renamed the RERF (Radiation effects and research foundation), funded equally by the United State of America and Japan. The RERF continues its work on genetics, cancer induction and other delayed effects of ionizing radiation .
Current concepts of radiation hazards
In the current context, it is believed that without proper precautions radiation sources are just as dangerous as they were earlier, or perhaps pose a greater potential danger because of their vast increase in use and also because a higher intensity of radiation production is possible with modern equipment.
In India, we are in a scenario of two groups of people, one with complete ignorance of radiation hazards, which comprise a vast majority and the other a small minority of educated patients who are terrified of even tiny radiation exposures. The latter group being more common in developed countries, are more sensitized and have even launched litigation suits against companies producing radioactive materials.
Interaction of radiation with matter:
There are three major ways in which radiation, especially x-rays is absorbed and results in ionization: the photoelectric effect, the Compton effect and pair production. At low energies (30 to 100 kev), as in diagnostic radiology, the photoelectric effect is important. In this process, the incident photon interacts with an electron in one of the outer shells of an atom (typically K, L, or M). If the energy of the photon is greater than the binding energy of the electron, then the electron is expelled from the orbit with a kinetic energy that is equal to the energy of the incident photon minus the binding energy of the electron. The photoelectric effect varies as a function of the cube of the atomic number of the material exposed (Z); this fact explains why bone is visualized much better than soft tissue on radiographs .
At higher energies, as used in therapeutic radiology, the Compton effect dominates. In this process, the incident photon interacts with an electron in an orbital shell. Part of the incident photon energy appears as kinetic energy of electrons and the residual energy continues as a less energetic deflected photon.
At energy levels above 1.02 MeV, the photons may be absorbed through pair production. In this process, both a positron and an electron are produced in the absorbing material. A positron has the same mass as an electron but has a positive instead of a negative charge. The positron travels a very short distance in the absorbing medium before it interacts with another electron. When that happens, the entire mass of both particles is converted to energy, with the emission of two photons in exactly opposite directions .
Biological effects of radiation
General principles of radiation effects on living organisms
When considering the effects of radiation on living organisms, it is important to keep the following general principles in mind:
1. The interaction of radiation in a cell is a probability function or a matter of chance, i.e., an interaction may or may not occur. Furthermore, the occurrence of an interaction does not necessarily mean that damage will result. In fact, damage is frequently repaired.
2. The initial deposition of energy occurs very rapidly, within 10-18 seconds.
3. Radiation deposits energy in a cell in a random fashion.
4. Radiation produces no unique changes in cells, tissues, or organs. The changes induced by radiation are indistinguishable from damage produced by other types of trauma.
5. The biological changes in cells, tissues, and organs do not appear immediately. They occur only after a period of time (latent period), ranging from hours,(e.g., after accidental overexposures to the total body, resulting in failure of organ system and death), to as long as years, (e.g., in the case of radiation-induced cancer) or even generations, (such as is the case if the damage occurs in a germ cell leading to heritable changes). The length of the latency period depends on factors related to the radiation, basically of radiation exposure, the dose as well as to biological characteristics of the cells irradiated and most importantly their rate of division and to the frequency of their rate of division .
Radiation may deposit energy directly within the critical target of the cell, which is the DNA; this type of action is known as the direct action. Biological effects of radiation including cell killing, mutagenesis and carcinogenesis are all due to damage to DNA, i.e. the direct action. Interaction of radiation with the other molecules in the cell is an indirect action. Indirect action is due to action on the major constituents of the cell, which are the water molecules. Radiation releases OH ions from water molecules, which cause the cell damage due to their oxidizing effect .
Mean lethal dose or LD50 - The lethal dose 50 or LD50 is a term borrowed from pharmacology and is defined as the dose of an agent that causes mortality in 50% of given population in a given time. For radiation, LD 50 has been estimated from the atomic bomb explosion at Hiroshima and Nagasaki and from accidental exposures. Based on these data and the observation that with medical support humans can survive a total body dose of 4 Gy, estimates of LD50 for humans is 3 to 4 Gy .
Pathology of Radiation Injury
Any tissue can express both acute and late symptoms of radiation damage, depending on the cell type which is the limiting function at that time. Irradiated cells die either a mitotic death which is also called reproductive failure. Mitotic death occurs when an irradiated cell attempts to undergo mitosis. Mitotic death can occur after relatively small doses of radiation. The other form of death is apoptosis or programmed cell death. Apoptosis is a natural form of cell death, which occurs spontaneously without a cytotoxic insult .
Acute responses to radiation therapy are seen in tissues with rapid turnover (gastrointestinal mucosa, bone marrow, skin, oropharyngeal and esophageal mucosa). Acute radiation damage leads to cell necrosis. In chronic radiation injury, atrophy, necrosis, ulceration, metaplasia, dysplasia or neoplasia can occur in epithelial and parenchymal cells. In the stromal tissue, changes that are seen are ; fibrosis, necrosis and presence of atypical fibroblasts. Arteries and capillaries show endothelial cell damage, thrombosis, rupture, myo-intimal proliferation and vasculitis. Small veins show intimal proliferation, fibrosis and veno occlusive disease (as in the liver) .
CLASSIFICATION OF RADIATION INJURY
Radiation effects are classified as : acute or chronic, involving somatic tissues or genetic information, and be directly proportional to dose ie deterministic (certainty) effects, or not directly proportional to dose ie stochastic effects.
a) Certainty or deterministic effects
• Related with certainty to a known dose of radiation
• Dose threshold exists
• Severity is dose related
b) Stochastic effects
• Random events without threshold
• Probability increases with dose.
• Severity may not be dose related
2. Genetic - are stochastic by their nature .
Deterministic effects have been documented from radiation accidents such as atomic bomb explosions and nuclear fall- outs and from patients undergoing radio- therapy.
Deterministic effects as documented from radiation accidents and from patients undergoing radio therapy :
Acute total-body irradiation - The data regarding the acute effects of total-body irradiation on humans come primarily from Japanese survivors of the atomic bomb, Marshall Islanders exposed to fall out radiation, victims of a few nuclear installation accidents, such as Chernobyl (in Ukraine) and patients in radiation therapy. Clinical manifestations depend on the total-body dose. At doses in excess of 100 Gy to the total body, death usually occurs within 24 to 48 hrs from neurologic and cardiovascular failure. This is known as the cerebrovascular syndrome. Because cerebrovascular damage cause death very quickly, the failure of other systems do not have time to develop.
At doses between 5 and 12 Gy, death may occur in a matter of days, as a result of the gastrointestinal syndrome. The symptoms during this period may include nausea, vomiting and prolonged diarrhea for several days, leading to dehydration, sepsis and death. Radiation workers and firefighters at Chernobyl are known to have died of the gastrointestinal syndrome.
At total-body doses between 2 and 8 Gy, death may occur several weeks after exposure and is due to effects on the bone marrow, which results in the hematopoietic syndrome. The full effect of radiation is not apparent until the mature hematopoietic cells are depleted. Death from the hematologic damage occurs at about 20 to 30 days after exposure and the risk of death continues over the next 30 days. Clinical symptoms during this period may include chills, fatigue and petechial hemorrhage. The threshold for this syndrome is 1 Gy. At Chernobyl, approximately 200 employees were exposed to radiation >1Gy and exhibited overt signs of the hemopoeitic syndrome ,.
Chronic radiation effects - These effects result from prolonged exposure of lower intensity or may appear as late effects in survivors of more acute exposures. These may be due to whole body or partial body irradiation.
Since deterministic effects are classically known from studies on patients undergoing radiotherapy, therefore, the threshold dose for a number of deterministic effects is known and is used by radiation oncologists in planning their treatment. However, an example of deterministic injury occurring in a radiodiagnostic setting, is a skin burn occurring to the angiographer after prolonged irradiation in a catheterization laboratory . Deterministic effects on the skin in the form of chronic skin scarring is also known in patients undergoing multiple angioplasties through the same skin port. Another example of chronic deterministic injury is radiation induced cataracts reported in angiographers .
Somatic certainty effects on organ systems ( as evaluated in patients on radiotherapy) :
Somatic certainty effects - As explained above, these can normally be related with certainty to a known dose of radiation and are not just a matter of probability.
Central Nervous System - Traditionally, the central nervous system (CNS) has been described as relatively resistant to radiation induced changes. When the human brain is treated with standard fractionation (1.8 to 2.0 Gy/d), acute reactions are seldom observed. Subacute CNS reactions to radiation treatment are more common. Mild encephalopathy and focal neurologic changes can occur after irradiation limited to the cranium. The effect of cranial irradiation is believed to be secondary to radiation effects on the replicating oligodendrocytes and possibly on the micro-vasculature. Post-irradiation pathology and associated clinical symptoms typically begin 6 to 36 months after radiation therapy. There effects are clearly related to the total dose and volume treated. A unique late effect of cranial irradiation combined with chemotherapy, known as leukoencephalopathy, has been described is a necrotizing reaction usually noted 4 to 12 months after combined treatment with methotrexate and cranial irradiation . Radiation necrosis occurs in 1% to 5% of patients after 55 to 60 gray doses, fractionated over 6 weeks; 75% of cases occur within 3 years .
Transverse myelitis after radiation treatment is a spinal cord reaction similar to cerebral necrosis. This syndrome consists of progressive and irreversible leg weakness and loss of bladder function and sensation referrable to a single spinal cord level. Flaccid paralysis eventually occurs. Symptoms can occur as early as 6 months after radiation treatment, but the usual time to onset is 12 to 24 months. Marcus and Million showed that at 45 Gy, the incidence of radiation myelitis is < 0.2% .
Skin - Skin reaction can be seen within 2 weeks of fractionated radiotherapy, a delay that correlates with the time required for cells to move from the basal to the keratinized layer of skin. Erythema is observed soon followed by dry desquamation .
A chronic reaction to radiation can be seen starting 6 to 12 months after irradiation. The epidermis is usually atrophic and it may be more easily injured than normal skin. The amount of interstitial fibrosis may also be increased. Hyperpigmentation of irradiated skin outlining the treatment field can be seen within a couple of months after completion of irradiation. The skin becomes thin and hair loss may be permanent .
Heart and blood vessels - Acute "pericarditis" may result from cardiac irradiation. The symptoms may include chest pain and fever, with or without pericardial effusion. Asymptomatic pericardial effusion may be the most common manifestation of radiation induced heart disease. Most patients with symptomatic radiation-induced constrictive pericarditis will have received more than 40 Gy to a large portion of the heart. The risk increases significantly with cardiac doses greater than 50 Gy. Chronic cardiac changes may have their onset from 6 months to several years after irradiation. The clinical symptoms may indicate chronic constrictive disease due to pericardial, myocardial and endocardial fibrosis - a pancarditis .
Lung - The clinical signs and symptoms of radiation pneumonitis may appear within 3 to 6 weeks if a large region of lung is irradiated to a dose above 25 Gy. An infiltrate outlining the treatment field may become evident on the chest x-ray. Permanent scarring that results in respiratory compromise may develop if the dose and the volume of lung irradiated are excessive.It has been established that at 8.2 Gy, there is a 5% incidence of lethal radiation induced pneumonitis which increases to 80% at 11 Gray ,.
Digestive Tract - The mucosa of the GI tract is a rapid renewal system, with dramatic mucosal changes appearing within 7 to 14 days . Clinical manifestations of acute radiation enteropathy are nausea and vomiting, diarrhea and cramping pain. Relevant factors contributing to the pathogenesis of diarrhea include malabsorption and alterations in the intestinal bacterial flora. The severity of symptoms, as in other anatomic areas, is proportional to the irradiated volume and the total dose. The symptoms of chronic radiation enteropathy include diarrhea, abdominal cramping, nausea, malabsorption, vomiting and obstruction. Progressive fibrosis, perforation, fistula formation and stenosis of the irradiated portion of the bowel can also occur during the chronic phase of radiation enteropathy. Most clinical manifestations of chronic changes occur between 6 months and 5 years after radiation therapy .
It has been reported that 6% of cases treated with 60 Gy in 6 weeks for carcinoma esophagus show changes in the pharynx/esophagus. In patients irradiated for abdominal lymphadenopathy, radiologic abnormalities are found in the stomach in 8.3% of patients treated with 40-60 Gy and in 16% when doses exceeded 60 gray. The incidence of small bowel injury is 15% to 25% if paraaortic irradiation doses were 50-55 Gy. However, 45-50 Gy was well tolerated. The terminal ileum is the most frequently symptomatically damaged part, as a result of the high turnover rate of the epithelial cells. Tolerance in the colorectal regions is considered higher. In patients receiving radiation therapy for cervical or prostatic cancer, the incidence of severe proctitis is reported to be 5% for 65-70 Gy; if the dose is increased to 75 Gy, 20% patients are found to be affected .
Haemopoeitic system - Fractionated radiation to a localised area of the marrow leads to a unique lesion of adipose tissue replacing the marrow, instead of fibrotic tissue as occurs in other organs. This change is recorded at a threshold dose greater than 50 Gy .
Eye -Cataract has been recorded at 2-8 Gray of single exposure .
Bladder - Radiation injury to the bladder generally becomes symptomatic 3 to 6 weeks after the start of treatment and symptoms usually subside 3 to 4 weeks after completion of radiation therapy. Cystoscopy often shows diffuse mucosal changes similar to those of acute cystitis. The late effects of high radiation doses to the bladder may include interstitial fibrosis, telangiectasia and ulceration. A contracted bladder may result from doses in excess of 60 Gy .
Testis and Ovaries - In general, type B spermatogonia are exquisitely sensitive to the effects of radiation. The type A spermatogonia are thought to be more resistant because their longer cell cycle time allows considerable variation in radiosensitivity among different phases of the cell cycle. Sertoli cells More Details and Leydig cells are less radiosensitive than the spermatogonia. The single dose required for permanent sterilization on normal human males is not clearly established but it is believed to be between 6 and 10 Gy . Low dose fractionated irradiation leads to decrease in sperm count. Regeneration of spermatogonia usually does not begin until 2 to 8 weeks after the injury ,.
The radiation dose necessary to induce ovarian failure is age dependent. A single dose of 3 to 4 Gy can induce amenorrhea in almost all women over 40 years of age. In young women, oogenesis is much less sensitive to radiation than spermatogenesis is in men .
Somatic stochastic effects
These are late effects which occur at random with no dose threshold. All stochastic effects are late but not all late effects are stochastic. The probability of their occurrence increases with increase in the absorbed dose but not their severity. The effects of shortening of life span and induction of malignancies are considered somatic stochastic effects
Shortening of life span - This is has been reported in laboratory mice. .
The incidence and the types of malignancies associated with radiation exposure are described below:
Leukemia - The incidence of leukemia in the survivors of the atomic bomb was 3 to 5 times higher than the expected incidence in the unexposed population. Two types of adult leukemias are associated with radiation exposure. These are acute and chronic myeloid leukemias. Radiation exposure during childhood results in an increased incidence of acute lymphatic leukemia. The latency period of leukemia is a minimum of 2 years, eaks at 7-12 yrs and returns to zero at about 30 years .
Other radiation induces cancers
Malignancies of skin, lung, bone, blood dyscrasias and meningiomas have been described. Data from female survivors of Japanese atomic bomb and Canadian studies on women screened for tuberculosis by fluoroscopy show an increased incidence of radiation induced breast cancer. Lung cancer is also more frequent in Japanese survivors of atomic bombs and miners exposed to radon and radioactive gas. Other malignancies known to be associated with radiation are osteosarcomas and thyroid carcinoma . A high incidence of thyroid carcinomas have been reported in children living in areas with high radioactive contamination from the Chernobyl accident .
Risk estimates for radiation induced cancer
The likelihood of developing radiation induced cancer is described as a "cancer risk". The risks are of two types : Absolute risk and relative risk.
Absolute risk - for developing cancer is defined as that in which the risk increases for a period of time and then decreases an example of this type of cancer risk is radiation induced leukemia.
Relative risk - risk increased by a constant factor for all ages. This type of risk may be applicable for other radiation induced cancers .
Evaluations of radiation induced cancer have been based on data from atomic bomb survivors of 1945, and is projected as a "lifetime risk" and this has been estimated for high dose rates of the atomic bomb to be 10 x 10-2 Sv-1 (0.1 per Sv). For radiation protection purposes the nominal risk is 5 x 10-2 Sv-1 (0.05 per Sv) for general population and 4 x 10-2 Sv-1 (0.04 per Sv) for occupational workers. At > 0.2 Gy doses, significant excesses of cancer have been documented. The nominal values of risk of cancer are risk for the whole body. However, the most sensitive organs are gonads (mainly for genetic effects), bone marrow, lungs, colon, stomach, breast, thyroid, liver and oesophagus. There is an increased incidence of leukemia and solid tumours in survivors of Hiroshima & Nagasaki. An increased incidence of leukemia is also observed in radiologists and patients irradiated for ankylosing spondylitis. An increased incidence of thyroid carcinoma has also been documented in children irradiated for enlarged thymus ,.
Mechanism of radiation induced cancer
There are 3 potential mechanisms, basically genetic in nature, by which radiation may induce changes leading to cancer : Check point genes that control cellular proliferation and differentiation may be disrupted, activation of oncogenes may occur, loss of supressor genes may induce cancer as explained in the following section .
Genetic mechanism of radiation induced cancers:
DNA and chromosomal changes can give rise to malignancies either by activation of oncogenes or by the loss of supressor genes. Oncogenes are mutated genes that are thought to be involved in the transformation of a normal cell to a malignant phenotype. Radiation can activate oncogenes through a number of mechanisms including point mutation, chromosomal rearrangement or chromosomal translocations. Suppressor genes are present in normal cells and normally prevent induction of tumours. If radiation results in loss of a suppressor gene chromosome, then it may become conducive to the expression of a malignant phenotype. Suppressor genes may also be involved in the change to a malignant phenotype via a chromosomal aberration .
Genetic effects of radiation
Radiation can either damage the DNA or effect the chromosome itself. Genetic effects on humans manifest as mutations leading to congenital defects in the offspring or causing malignancies. The genetic effects of radiation are evaluated on the basis of their mutational effects which is expressed as the "genetic doubling dose". Genetic doubling dose is an estimate of the amount of acute radiation which will double the spontaneous mutation rate or will cause an increase in the mutation rate which is equal to the number of spontaneous mutations which normally occur . The most common genetic effects such as autosomal and X linked changes and chromosomal alterations in an exposed population have been estimated to be occurring at 1 x 10-2 Sv-1 (0.01 mutations per Sv) ,.
Neel et al , analysed the data on children of survivors of atomic bomb in Hiroshima and Nagasaki along with children of suitable control population. Their analysis showed that humans are less sensitive to genetic effects of radiation than was earlier presumed on the basis of experimental studies with mice. According to these investigators, the genetic doubling radiation dose for acute radiation is 1.7 to 2.2 Sv and for chronic radiation between 3.4 and 4.5 Sv. It is believed that radiation does not create new mutations but only increases the frequency of mutations occurring naturally in the general population. The dosage required to double this base line mutation rate is between 50 to 100 rads (0.5 to 1 gray). If 10,000 persons were exposed to 1 rad (0.01 gray), 10 to 40 new genetic mutations would be induced ,.
Patho-physiology of genetic effects of radiation:
1. Radiation damage to DNA
It is generally accepted that DNA is a critical target for radiation. DNA consists of two strands that form a double helix. The backbone of each strand is made up of sugar moieties and phosphate groups, which serve as the framework for the four bases. The order of these bases on the sugar-phosphate backbone spells out the genetic code.
Radiation can damage either the backbone of DNA, producing strand breaks, or it can produce alterations or loss of bases. Strand breaks may occur in only one of the strands (a single strand break, SSB), or in both strands (a double strand break, DSB). SSBs are more readily repaired, most likely because they can use the opposite unbroken strand as a template. DSBs, particularly if they are opposite each other, or separated by only a few base pairs, are repaired less efficiently and at a slower rate than SSBs. DSBs are known to be correlated with higher rate of cell death, as compared to SSBs. Ataxia telangiectasia is a rare genetic disorder associated with deficiency of DNA repair .
2. Chromosomal Effects
Radiation produces breaks in chromosomes, termed aberrations, which can be observed. Aberrations are further specified as either chromosomes or chromatid aberrations depending on whether they occur before or after DNA synthesis. Chromosome aberrations are those that occur early in interphase, before the genetic material is duplicated. In this situation, the break occurs in only one strand of the DNA and is then duplicated during DNA synthesis. Aberrations occurring after DNA has been duplicated, when the chromatin consists of two strands, are termed chromatid aberrations.
The general consequences of these breaks are as follows :
1. The ends of the same chromosome may rejoin, a process called restitution. This causes no changes.
2. The sticky end of one chromosome may join with that of another, leading to re-assortment of the genetic material and an aberration visible at the net metaphase.
3. The broken ends may not rejoin. The genetic material contained in the acentric fragment will be lost from the cell.
Loss of a significant amount of genetic material results in cell death, loss of a lesser amount of genetic material is a "deletion." Chromosomal aberrations that result in a rearrangement of the sequence of the genetic code carried by the chromosome can have profound effects on the cell. Chromosomal aberrations are associated with certain malignancies: Burkitt's lymphoma was the first tumor shown to involve a translocation of a specific gene. Other tumors include acute promyelocytic leukemia and ovarian cancer. Tumors associated with deletions include small cell lung cancer, neuroblastoma, retinoblastoma and Wilms' tumor .
Effects of radiation on fetus
A report by the International Commission on Radiological Protection (ICRP) states "diagnostic and therapeutic procedures causing exposure of the abdomen of women likely to be pregnant should be avoided unless there are strong clinical indications". The best approximation of the fetal dose is the calculation of the dose delivered to the uterus and calculations on fetal effects are based on these (uterine) doses .
Effects on the fetus may be both deterministic and stochastic.
Deterministic effects on the fetus:
Deterministic effects results from the killing of cells and there is a threshold dose. Examples are fetal death, gross malformations, mental retardation and growth retardation. Fetal malformations reported in the CNS are exencephaly, microcephaly, mental retardation, skull malformations and hydrocephaly. The ocular malformations reported with radiation are absence of eyes, microphthalmia, absence of lens and cataract. Skeletal malformations are stunting, cleft palate, club feet, deformed arms and spina bifida. Other malformations are genital deformities ,.
The incidence of fetal malformations is 1 out of 2 for children irradiated in utero at therapeutic doses .
Effects on growth have thresholds of approximately > 0.1 Gy ( 5-10 cGy). Effects on CNS & risk of mental retardation and lowering of I/Q are deterministic with thresholds estimated at 0.1 to 0.2 Gy and the most sensitive period is 8-15 weeks of gestation ,. Neel et al studied the Untoward pregnancy outcome or UPO (Child with major congenital anomalies or still birth or death of the child within 2 weeks of birth) in children of parents exposed to atomic bomb radiation, they found that there was a larger number of UPOs in the progeny of the irradiated parents as compared to unexposed parents. This UPO was observed to be higher in male progeny, showing an increase with increasing maternal age and a decrease with increasing paternal age ,.
Effects of radiation on various stages of the fetus: Radiation during the pre implantation period can lead to death of the embryo and the incidence is 6.9% with a dose of 0.5 Gy. During 9-60 days post conception, at a threshold dose of 10 cGy the incidence of fetal mortality is 4.8% and the risk of malformation is 0.5% per cGy. At 61-104 days post- conception the threshold for lethality is 0.5 Gy and radiation at this stage leads to either to fetal death or to brain malformations. At 105-175 days post conception the defects are mental retardation, small head size and growth retardation, at this stage the threshold for growth retardation is 0.5 Gy. At more than 175 days post conception the risks for malformation and mental retardation are negligible. .
Stochastic effects are caused by mutations in a cell or in a small group of cells.
It has been estimated that radiation doses to the order of 10 mGy received by the fetus in utero produces an increased risk of childhood leukemia at the rate of 6% per Gy. It has been found from various studies that the relative risk of cancer induction is 1.29 and 1.30 respectively when exposure occurs in the 2nd and 3rd trimester but is higher ie 3.19 when it occurs in the first trimester and is highest in the first 8 weeks after conception when it is 4.60 . In Neel et al's study on the incidence of cancer in children whose parents were exposed to atomic bomb radiation, 43 out of 31,150 children of exposed parents had cancer, as opposed to 49 out of 41,066 children of unexposed parents, ie an incidence of 0.14% in exposed versus 0.12% in unexposed parents .
The dose rate required in utero to double the base line mutation rate is 50-100 Rads (0.5-1 gray). The risk of genetic mutations is 0.024 to 0.099% per cGy .
Safety of radiographic imaging during pregnancy
Maternal illness during pregnancy is not uncommon and sometimes requires radiographic imaging for proper diagnosis and treatment. The patient and her physician may be concerned about potential harm to the fetus from radiation exposure. The effects on the fetus are radiation induced teratogenesis, malignancies and genetic mutations. The effects on growth are deterministic effects and have a threshold of approximately 0.1 Gy. For mental retardation and lowering of IQ the threshold is perhaps 0.1 to 0.2 Gy and the most sensitive period is 8-17 weeks of gestation. It is estimated that in routine diagnostic imaging the radiation doses rarely reach the risk limits and therefore the risks to the developing fetus are quite small . The accepted cumulative dose of ionizing radiation during pregnancy is 5 rad (0.05 gray or 50m gray or 50mSv), and no single diagnostic study exceeds this maximum. For example, the amount of exposure to the fetus from a two-view chest x-ray of the mother is only 0.00007 rad (0.0000007 Gray/ or 0.0007m gray or 0.0007m Sv). However, since the most sensitive time period for central nervous system teratogenesis is between
8 to 17 weeks of gestation, non-urgent radiological testing should be avoided during this time. As discussed above, the rare consequences of prenatal radiation exposure include a slight increase in the incidence of childhood leukemia and, possibly, a very small change in the frequency of genetic mutations. Such exposure is not usually an indication for pregnancy termination. Therefore, appropriate counseling of pregnant patients before radiological studies are performed is critical ,.
The pregnant radiation worker:
The NCRP (National Radiological Protection Board of America ) recommends that the dose to the fetus in female radiation workers should not exceed 0.5 m Sv per month (i.e. 0.5 m Gy or 0.05 Rad per month for Xrays ). The ICRP ( International Council for Radiation Protection) recommends that the total dose to the abdomen of the mother should not exceed 2 mSv during entire pregnancy .
SAFETY OF PELVIMETRY TECHNIQUES
Assessment of the maternal pelvic dimensions may be required when a vaginal delivery is being considered for a breech presentation, or for any obstetric setting in which a reduced pelvic dimension is suspected. It is recommended that MRI should be used when ever possible as it is the safest technique in pregnancy. However, if CT is used then a single lateral scanogram at the lowest mAs and minimal scan length is the recommended technique as this gives the lowest radiation dose. If CT is not available, a single lateral view using an air gap technique without a grid, with good coning and fast film screen combination is the best alternative to a single view CT technique .
BIOLOGICAL EFFECTS OF PARENTAL PRECONCEPTION IRRADIATION
Recent epidemiological studies and reviews from different parts of the world by various Investigators, have shown that paternal preconception irradiation ( PPI ) is not associated with an increased risk of childhood cancer as was reported in earlier series ,. However, Goldstein and Murphy have reported that preconception maternal irradiation in therapeutic doses gives rise to defects in 1 out of 10 or 11 exposed children .
| Conclusion|| |
X-ray absorption unit is expressed in the current SI system by the unit gray which is equivalent to 1 Joule of energy per kg of irradiated tissue. The unit Sievert is used for expressing the biological effectiveness of the absorbed dose of radiation. This is obtained by the product of gray and qualifying factor. The qualifying factor for X-rays and Gamma rays is 1. Natural sources of radiation account for significant radiation exposure during a person's life time and the annual effective dose in the US has been estimated to be 3.6 mSv. Somatic certainty effects which have been evaluated on patients undergoing radiotherapy have shown that the tissues most sensitive to radiation damage are bone marrow, eye and gonads. From these studies on radiotherapy patients, the threshold doses are estimated as 1 gray for bone marrow, 2-8 grays for eye, 3-4 grays to elicit ovulation failure in middle aged women and 6-10 grays causes failure of spermatogenesis. It has been found that the GIT is sensitive at 75 grays, the brain beyond 55-60 grays, the spinal cord at 45 grays, the heart at 40-50 grays and the lung at 11 grays. Radiation induced chromosomal mutations and carcinogenesis are significant stochastic effects. It is estimated that the genetic doubling dose for radiation induced mutations is 1.7 to 2.2 Sv for acute radiation and between 3.4 - 4.5 Sv for chronic radiation. The nominal values of risk of cancer are 0.05 per Sv for general population and 0.04 per Sv for occupational workers. Malignancies associated with radiation exposure are leukemias, carcinoma of lung, breast, thyroid and skin and meningiomas and osteosarcomas. Effects on the fetus are both deterministic and stochastic which lead to teratogenesis and childhood malignancies. The accepted cumulative dose of ionising radiation during pregnancy is 5 rads (0.05 gray OR 50 m gray OR 50mSv). Although, the amount of exposure to the fetus from a two view chest radiograph of the mother is only 0.00007 rads (0.0007 m gray OR mSv), it is recommended that non urgent radiological testing should not be done between 8-17 weeks of gestation, which is the most sensitive period for organogenesis. Although the first 8 weeks post- conception are the most sensitive to radiation for induction of malignancies and genetic mutations, the risk is too insignificant, at doses delivered in routine radiological procedures. It is the responsibility of every radiologist to be aware of units of radiation measurement, doses and the various biological effects. Although the probability of the occurrence of these biological effects appears to be low in terms of statistics, however it must be remembered that whenever these consequences are manifest, they are grave.
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S B Grover
Department of Radiology, Safdarjang Hospital, New Delhi-110029
Source of Support: None, Conflict of Interest: None
[Figure - 1]
[Table - 1], [Table - 2], [Table - 3]
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