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Radiosensitivity is the relative susceptibility of cells, tissues, organs or organisms to the harmful effect of ionizing radiation.
| | This article needs additional citations for verification .(November 2009) |
Radiosensitivity is the relative susceptibility of cells, tissues, organs or organisms to the harmful effect of ionizing radiation.
Cells are least sensitive when in the S phase, then the G1 phase, then the G2 phase, and most sensitive in the M phase of the cell cycle. This is described by the 'law of Bergonié and Tribondeau', formulated in 1906: X-rays are more effective on cells which have a greater reproductive activity. [1] [2]
From their observations, they concluded that quickly dividing tumor cells are generally more sensitive than the majority of body cells. This is not always true. Tumor cells can be hypoxic and therefore less sensitive to X-rays because most of their effects are mediated by the free radicals produced by ionizing oxygen.
It has meanwhile been shown that the most sensitive cells are those that are undifferentiated, well nourished, dividing quickly and highly active metabolically. Amongst the body cells, the most sensitive are spermatogonia and erythroblasts, epidermal stem cells, gastrointestinal stem cells. [3] The least sensitive are nerve cells and muscle fibers.
Very sensitive cells are also oocytes and lymphocytes, although they are resting cells and do not meet the criteria described above. The reasons for their sensitivity are not clear.
There also appears to be a genetic basis for the varied vulnerability of cells to ionizing radiation. [4] This has been demonstrated across several cancer types and in normal tissues. [5] [6]
The damage to the cell can be lethal (the cell dies) or sublethal (the cell can repair itself). Cell damage can ultimately lead to health effects which can be classified as either Tissue Reactions or Stochastic Effects according to the International Commission on Radiological Protection.
Tissue reactions have a threshold of irradiation under which they do not appear and above which they typically appear. Fractionation of dose, dose rate, the application of antioxidants and other factors may affect the precise threshold at which a tissue reaction occurs. Tissue reactions include skin reactions (epilation, erythema, moist desquamation), cataracts, circulatory disease, and other conditions. Seven proteins were discovered in a systematic review, which correlated with radiosensitivity in normal tissues: γH2AX, TP53BP1, VEGFA, CASP3, CDKN2A, IL6, and IL1B. [7] [8]
Stochastic effects do not have a threshold of irradiation, are coincidental, and cannot be avoided. They can be divided into somatic and genetic effects. Among the somatic effects, secondary cancer is the most important. It develops because radiation causes DNA mutations directly and indirectly. Direct effects are those caused by ionizing particles and rays themselves, while the indirect effects are those that are caused by free radicals, generated especially in water radiolysis and oxygen radiolysis. The genetic effects confer the predisposition of radiosensitivity to the offspring. [9] The process is not well understood yet.
For decades, the main cellular target for radiation induced damage was thought to be the DNA molecule. [10] This view has been challenged by data indicating that in order to increase survival, the cells must protect their proteins, which in turn repair the damage in the DNA. [11] An important part of protection of proteins (but not DNA) against the detrimental effects of reactive oxygen species (ROS), which are the main mechanism of radiation toxicity, is played by non-enzymatic complexes of manganese ions and small organic metabolites. [11] These complexes were shown to protect the proteins from oxidation in vitro [12] and also increased radiation survival in mice. [13] An application of the synthetically reconstituted protective mixture with manganese was shown to preserve the immunogenicity of viral and bacterial epitopes at radiation doses far above those necessary to kill the microorganisms, thus opening a possibility for a quick whole-organism vaccine production. [14] The intracellular manganese content and the nature of complexes it forms (both measurable by electron paramagnetic resonance) were shown to correlate with radiosensitivity in bacteria, archaea, fungi and human cells. [15] An association was also found between total cellular manganese contents and their variation, and clinically inferred radioresponsiveness in different tumor cells, a finding that may be useful for more precise radiodosages and improved treatment of cancer patients. [16]
Radiation therapy or radiotherapy is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body, and have not spread to other parts. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a radiation oncologist.
The sievert is a unit in the International System of Units (SI) intended to represent the stochastic health risk of ionizing radiation, which is defined as the probability of causing radiation-induced cancer and genetic damage. The sievert is important in dosimetry and radiation protection. It is named after Rolf Maximilian Sievert, a Swedish medical physicist renowned for work on radiation dose measurement and research into the biological effects of radiation.
The therapeutic index is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.
Deinococcota is a phylum of bacteria with a single class, Deinococci, that are highly resistant to environmental hazards, also known as extremophiles. These bacteria have thick cell walls that give them gram-positive stains, but they include a second membrane and so are closer in structure to those of gram-negative bacteria.
Desiccation is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic substance that induces or sustains such a state in its local vicinity in a moderately sealed container.
The linear no-threshold model (LNT) is a dose-response model used in radiation protection to estimate stochastic health effects such as radiation-induced cancer, genetic mutations and teratogenic effects on the human body due to exposure to ionizing radiation. The model statistically extrapolates effects of radiation from very high doses into very low doses, where no biological effects may be observed. The LNT model lies at a foundation of a postulate that all exposure to ionizing radiation is harmful, regardless of how low the dose is, and that the effect is cumulative over lifetime.
Radiation hormesis is the hypothesis that low doses of ionizing radiation are beneficial, stimulating the activation of repair mechanisms that protect against disease, that are not activated in absence of ionizing radiation. The reserve repair mechanisms are hypothesized to be sufficiently effective when stimulated as to not only cancel the detrimental effects of ionizing radiation but also inhibit disease not related to radiation exposure. It has been a mainstream concept since at least 2009.
Radioresistance is the level of ionizing radiation that organisms are able to withstand.
Radiobiology is a field of clinical and basic medical sciences that involves the study of the effects of ionizing radiation on living things, in particular health effects of radiation. Ionizing radiation is generally harmful and potentially lethal to living things but can have health benefits in radiation therapy for the treatment of cancer and thyrotoxicosis. Its most common impact is the induction of cancer with a latent period of years or decades after exposure. High doses can cause visually dramatic radiation burns, and/or rapid fatality through acute radiation syndrome. Controlled doses are used for medical imaging and radiotherapy.
In radiobiology, the relative biological effectiveness is the ratio of biological effectiveness of one type of ionizing radiation relative to another, given the same amount of absorbed energy. The RBE is an empirical value that varies depending on the type of ionizing radiation, the energies involved, the biological effects being considered such as cell death, and the oxygen tension of the tissues or so-called oxygen effect.
Deinococcus radiodurans is a bacterium, an extremophile and one of the most radiation-resistant organisms known. It can survive cold, dehydration, vacuum, and acid, and therefore is known as a polyextremophile. It has been listed as the world's toughest known bacterium in The Guinness Book Of World Records.
The abscopal effect is a hypothesis in the treatment of metastatic cancer whereby shrinkage of untreated tumors occurs concurrently with shrinkage of tumors within the scope of the localized treatment. R.H. Mole proposed the term “abscopal” in 1953 to refer to effects of ionizing radiation “at a distance from the irradiated volume but within the same organism.”
Exposure to ionizing radiation is known to increase the future incidence of cancer, particularly leukemia. The mechanism by which this occurs is well understood, but quantitative models predicting the level of risk remain controversial. The most widely accepted model posits that the incidence of cancers due to ionizing radiation increases linearly with effective radiation dose at a rate of 5.5% per sievert; if correct, natural background radiation is the most hazardous source of radiation to general public health, followed by medical imaging as a close second. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by ultraviolet radiation. Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been investigated as a possible carcinogen by the WHO's International Agency for Research on Cancer, but to date, no evidence of this has been observed.
Studies with protons and HZE nuclei of relative biological effectiveness for molecular, cellular, and tissue endpoints, including tumor induction, demonstrate risk from space radiation exposure. This evidence may be extrapolated to applicable chronic conditions that are found in space and from the heavy ion beams that are used at accelerators.
Deinococcus geothermalis is a non-pathogenic, sphere-shaped, Gram-positive, heterotrophic bacterium, where geothermalis means 'hot earth' or 'hot springs'. This bacterium was first obtained from the hot springs of Agnano, Naples, Italy and São Pedro do Sul, Portugal. It resides primarily in hot springs and in deep ocean environments.
Deinococcus frigens is a species of low temperature and drought-tolerating, UV-resistant bacteria from Antarctica. It is Gram-positive, non-motile and coccoid-shaped. Its type strain is AA-692. Individual Deinococcus frigens range in size from 0.9-2.0 μm and colonies appear orange or pink in color. Liquid-grown cells viewed using phase-contrast light microscopy and transmission electron microscopy on agar-coated slides show that isolated D. frigens appear to produce buds. Comparison of the genomes of Deiococcus radiodurans and D. frigens have predicted that no flagellar assembly exists in D. frigens.
Deinococcus marmoris is a Gram-positive bacterium isolated from Antarctica. As a species of the genus Deinococcus, the bacterium is UV-tolerant and able to withstand low temperatures.
Radiation exposure is a measure of the ionization of air due to ionizing radiation from photons. It is defined as the electric charge freed by such radiation in a specified volume of air divided by the mass of that air. As of 2007, "medical radiation exposure" was defined by the International Commission on Radiological Protection as exposure incurred by people as part of their own medical or dental diagnosis or treatment; by persons, other than those occupationally exposed, knowingly, while voluntarily helping in the support and comfort of patients; and by volunteers in a programme of biomedical research involving their exposure. Common medical tests and treatments involving radiation include X-rays, CT scans, mammography, lung ventilation and perfusion scans, bone scans, cardiac perfusion scan, angiography, radiation therapy, and more. Each type of test carries its own amount of radiation exposure. There are two general categories of adverse health effects caused by radiation exposure: deterministic effects and stochastic effects. Deterministic effects are due to the killing/malfunction of cells following high doses; and stochastic effects involve either cancer development in exposed individuals caused by mutation of somatic cells, or heritable disease in their offspring from mutation of reproductive (germ) cells.
Ionizing radiation can cause biological effects which are passed on to offspring through the epigenome. The effects of radiation on cells has been found to be dependent on the dosage of the radiation, the location of the cell in regards to tissue, and whether the cell is a somatic or germ line cell. Generally, ionizing radiation appears to reduce methylation of DNA in cells.
In biochemistry, the oxygen effect refers to a tendency for increased radiosensitivity of free living cells and organisms in the presence of oxygen than in anoxic or hypoxic conditions, where the oxygen tension is less than 1% of atmospheric pressure.