The biological effects of radiation result primarily from damage to DNA. There are three effects ... more The biological effects of radiation result primarily from damage to DNA. There are three effects of concern to the radiologist that determine the need for radiation protection and the dose principle of ALARA (As Low As Reasonably Achievable). (1) Heritable effects. These were thought to be most important in the 1950s, but concern has declined in recent years. The current ICRP risk estimate is very small at 0.2%/Sv. (2) Effects on the developing embryo and fetus include weight retardation, congenital anomalies, microcephaly and mental retardation. During the sensitive period of 8 to 15 weeks of gestation, the risk estimate for mental retardation is very high at 40%/Sv, but because it is a deterministic effect, there is likely to be a threshold of about 200 mSv. (3) Carcinogenesis is considered to be the most important consequence of low doses of radiation, with a risk of fatal cancer of about 5%/Sv, and is therefore of most concern in radiology. Our knowledge of radiation carcinogenesis comes principally from the 60-year study of the A-bomb survivors. The use of radiation for diagnostic purposes has increased dramatically in recent years. The annual collective population dose has increased by 750% since 1980 to 930,000 person Sv. One of the principal reasons is the burgeoning use of CT scans. In 2006, more than 60 million CT scans were performed in the U.S., with about 6 million of them in children. As a rule of thumb, an abdominal CT scan in a 1-year-old child results in a life-time mortality risk of about one in a thousand. While the risk to the individual is small and acceptable when the scan is clinically justified, even a small risk when multiplied by an increasingly large number is likely to produce a significant public health concern. It is for this reason that every effort should be made to reduce the doses associated with procedures such as CT scans, particularly in children, in the spirit of ALARA.
Page 1. Sixth Edition Eric J. Hall • Amato J. Giaccia CllLLippincott Williams & Wilkins a Wal... more Page 1. Sixth Edition Eric J. Hall • Amato J. Giaccia CllLLippincott Williams & Wilkins a Walters Kluwer business Page 2. Page 3. Page 4. Page 5. RADIOBIOLOGY FOR THE RADIOLOGIST SIXTH EDITION This One AXQG-A4J-A3F4 Page 6. Page 7. ...
Risk estimates derived from epidemiological studies of exposed populations, as well as the maximu... more Risk estimates derived from epidemiological studies of exposed populations, as well as the maximum permissible doses allowed for occupational exposure and exposure of the public to ionizing radiation are all based on the assumption that the human population is uniform in its radiosensitivity, except for a small number of individuals, such as ATM homozygotes who are easily identified by their clinical symptoms. The hypothesis upon which this proposal is based is that the human population is not homogeneous in radiosensitiviry, but that radiosensitive sub-groups exist which are not easy to identify. These individuals would suffer an increased incidence of detrimental radiation effects, and distort the shape of the dose response relationship. The radiosensitivity of these groups depend on the expression levels of specific proteins. The plan was to investigate the effect of 3 relatively rare, high penetrate genes available in mice, namely Atm, mRad9 & Brca1. The purpose of radiation protection is to prevent! deterministic effects of clinical significance and limit stochastic effects to acceptable levels. We plan, therefore to compare with wild type animals the radiosensitivity of mice heterozygous for each of the genes mentioned above, as well as double heterozygotes for pairs of genes, using two biological endpoints: a) Ocular cataracts as an important and relevant deterministic effect, and b) Oncogenic transformation in cultured embryo fibroblasts, as a surrogate for carcinogenesis, the most relevant stochastic effect.
Proceedings of The National Academy of Sciences, 2000
Ever since the discovery of X-rays was made by Rö ntgen more than a hundred years ago, it has alw... more Ever since the discovery of X-rays was made by Rö ntgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear͞extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A L cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 M dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.
The bystander effect refers to the induction of biological effects in cells that are not directly... more The bystander effect refers to the induction of biological effects in cells that are not directly traversed by a charged particle. The data available concerning the bystander effect fall into two quite separate categories, and it is not certain that the two groups of experiments are addressing the same phenomenon. First, there are experiments involving the transfer of medium from irradiated cells, which results in a biological effect in unirradiated cells. Second, there is the use of sophisticated single particle microbeams, which allow specific cells to be irradiated and biological effects studied in their neighbors; in this case communication is by gap junction. Medium transfer experiments have shown a bystander effect for cell lethality, chromosomal aberrations and cell cycle delay. The type of cell, epithelial vs. fibroblast, appears to be important. Experiments suggest that the effect is due to a molecule secreted by irradiated cells, which is capable of transferring damage to distant cells. Use of a single microbeam has allowed the demonstration of a bystander effect for chromosomal aberrations, cell lethality, mutation, and oncogenic transformation. When cells are in close contact, allowing gap junction communication, the bystander effect is a much larger magnitude than the phenomenon demonstrated in medium transfer experiments. A bystander effect has been demonstrated for both high- and low-LET radiations but it is usually larger for densely ionizing radiation such as alpha particles. Experiments have not yet been devised to demonstrate a comparable bystander effect on a three-dimensional normal tissue. Bystander studies imply that the target for the biological effects of radiation is larger than the cell and this could make a simple linear extrapolation of radiation risks from high to low doses of questionable validity.
T he advent of computed tomography (ct) has revolutionized diagnostic radiology. Since the incept... more T he advent of computed tomography (ct) has revolutionized diagnostic radiology. Since the inception of CT in the 1970s, its use has increased rapidly. It is estimated that more than 62 million CT scans per year are currently obtained in the United States, including at least 4 million for children. 1 By its nature, CT involves larger radiation doses than the more common, conventional x-ray imaging procedures . We briefly review the nature of CT scanning and its main clinical applications, both in symptomatic patients and, in a more recent development, in the screening of asymptomatic patients. We focus on the increasing number of CT scans being obtained, the associated radiation doses, and the consequent cancer risks in adults and particularly in children. Although the risks for any one person are not large, the increasing exposure to radiation in the population may be a public health issue in the future.
The biological effects of radiation result primarily from damage to DNA. There are three effects ... more The biological effects of radiation result primarily from damage to DNA. There are three effects of concern to the radiologist that determine the need for radiation protection and the dose principle of ALARA (As Low As Reasonably Achievable). (1) Heritable effects. These were thought to be most important in the 1950s, but concern has declined in recent years. The current ICRP risk estimate is very small at 0.2%/Sv. (2) Effects on the developing embryo and fetus include weight retardation, congenital anomalies, microcephaly and mental retardation. During the sensitive period of 8 to 15 weeks of gestation, the risk estimate for mental retardation is very high at 40%/Sv, but because it is a deterministic effect, there is likely to be a threshold of about 200 mSv. (3) Carcinogenesis is considered to be the most important consequence of low doses of radiation, with a risk of fatal cancer of about 5%/Sv, and is therefore of most concern in radiology. Our knowledge of radiation carcinogenesis comes principally from the 60-year study of the A-bomb survivors. The use of radiation for diagnostic purposes has increased dramatically in recent years. The annual collective population dose has increased by 750% since 1980 to 930,000 person Sv. One of the principal reasons is the burgeoning use of CT scans. In 2006, more than 60 million CT scans were performed in the U.S., with about 6 million of them in children. As a rule of thumb, an abdominal CT scan in a 1-year-old child results in a life-time mortality risk of about one in a thousand. While the risk to the individual is small and acceptable when the scan is clinically justified, even a small risk when multiplied by an increasingly large number is likely to produce a significant public health concern. It is for this reason that every effort should be made to reduce the doses associated with procedures such as CT scans, particularly in children, in the spirit of ALARA.
Page 1. Sixth Edition Eric J. Hall • Amato J. Giaccia CllLLippincott Williams & Wilkins a Wal... more Page 1. Sixth Edition Eric J. Hall • Amato J. Giaccia CllLLippincott Williams & Wilkins a Walters Kluwer business Page 2. Page 3. Page 4. Page 5. RADIOBIOLOGY FOR THE RADIOLOGIST SIXTH EDITION This One AXQG-A4J-A3F4 Page 6. Page 7. ...
Risk estimates derived from epidemiological studies of exposed populations, as well as the maximu... more Risk estimates derived from epidemiological studies of exposed populations, as well as the maximum permissible doses allowed for occupational exposure and exposure of the public to ionizing radiation are all based on the assumption that the human population is uniform in its radiosensitivity, except for a small number of individuals, such as ATM homozygotes who are easily identified by their clinical symptoms. The hypothesis upon which this proposal is based is that the human population is not homogeneous in radiosensitiviry, but that radiosensitive sub-groups exist which are not easy to identify. These individuals would suffer an increased incidence of detrimental radiation effects, and distort the shape of the dose response relationship. The radiosensitivity of these groups depend on the expression levels of specific proteins. The plan was to investigate the effect of 3 relatively rare, high penetrate genes available in mice, namely Atm, mRad9 & Brca1. The purpose of radiation protection is to prevent! deterministic effects of clinical significance and limit stochastic effects to acceptable levels. We plan, therefore to compare with wild type animals the radiosensitivity of mice heterozygous for each of the genes mentioned above, as well as double heterozygotes for pairs of genes, using two biological endpoints: a) Ocular cataracts as an important and relevant deterministic effect, and b) Oncogenic transformation in cultured embryo fibroblasts, as a surrogate for carcinogenesis, the most relevant stochastic effect.
Proceedings of The National Academy of Sciences, 2000
Ever since the discovery of X-rays was made by Rö ntgen more than a hundred years ago, it has alw... more Ever since the discovery of X-rays was made by Rö ntgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear͞extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A L cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 M dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.
The bystander effect refers to the induction of biological effects in cells that are not directly... more The bystander effect refers to the induction of biological effects in cells that are not directly traversed by a charged particle. The data available concerning the bystander effect fall into two quite separate categories, and it is not certain that the two groups of experiments are addressing the same phenomenon. First, there are experiments involving the transfer of medium from irradiated cells, which results in a biological effect in unirradiated cells. Second, there is the use of sophisticated single particle microbeams, which allow specific cells to be irradiated and biological effects studied in their neighbors; in this case communication is by gap junction. Medium transfer experiments have shown a bystander effect for cell lethality, chromosomal aberrations and cell cycle delay. The type of cell, epithelial vs. fibroblast, appears to be important. Experiments suggest that the effect is due to a molecule secreted by irradiated cells, which is capable of transferring damage to distant cells. Use of a single microbeam has allowed the demonstration of a bystander effect for chromosomal aberrations, cell lethality, mutation, and oncogenic transformation. When cells are in close contact, allowing gap junction communication, the bystander effect is a much larger magnitude than the phenomenon demonstrated in medium transfer experiments. A bystander effect has been demonstrated for both high- and low-LET radiations but it is usually larger for densely ionizing radiation such as alpha particles. Experiments have not yet been devised to demonstrate a comparable bystander effect on a three-dimensional normal tissue. Bystander studies imply that the target for the biological effects of radiation is larger than the cell and this could make a simple linear extrapolation of radiation risks from high to low doses of questionable validity.
T he advent of computed tomography (ct) has revolutionized diagnostic radiology. Since the incept... more T he advent of computed tomography (ct) has revolutionized diagnostic radiology. Since the inception of CT in the 1970s, its use has increased rapidly. It is estimated that more than 62 million CT scans per year are currently obtained in the United States, including at least 4 million for children. 1 By its nature, CT involves larger radiation doses than the more common, conventional x-ray imaging procedures . We briefly review the nature of CT scanning and its main clinical applications, both in symptomatic patients and, in a more recent development, in the screening of asymptomatic patients. We focus on the increasing number of CT scans being obtained, the associated radiation doses, and the consequent cancer risks in adults and particularly in children. Although the risks for any one person are not large, the increasing exposure to radiation in the population may be a public health issue in the future.
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