Inorganic Chemistry

Effect of Radioactivity on cell proliferation

Sandhya Tiwari

Index
1. Introduction 2. Radiation 3. Ionisation 4. How ionisation affects cells 5. Which cells are sensitive to radiation 6. Effect of radiations on cells 7. Effect of radiations on tumour 8. Biological Effects

Introduction

Radiation Causes Ionizations of atoms which may affect molecules which may affect cells which may affect tissues which may affect organs which may affect the whole body. Although we tend to think of biological effects in terms of the effect of radiation on living cells, in reality, ionizing radiation, by definition, interacts only with atoms by a process called ionization. Thus, all biological damage effects begin with the consequence of radiation interactions with the atoms forming the cells. As a result, radiation effects on humans proceed from the lowest to the highest levels are noted. Even though all subsequent biological effects can be traced back to the interaction of radiation with atoms, there are two mechanisms by which radiation ultimately affects cells. These two mechanisms are commonly called direct and indirect effects If radiation interacts with the atoms of the DNA molecule, or some other cellular component critical to the survival of the cell, it is referred to as a direct effect. Such an interaction may affect the ability of the cell to reproduce and, thus, survive. If enough atoms are affected such that the chromosomes do not replicate properly, or if there is significant alteration in the information carried by the DNA molecule, then the cell may be destroyed by direct interference with its life-sustaining system. If a cell is exposed to radiation, the probability of the radiation interacting with the DNA molecule is very small since these critical components make up such a small part of the cell. However, each cell, just as is the case for the human body, is mostly water. Therefore, there is a much higher probability of radiation interacting with the water that makes up most of the cells volume. When radiation interacts with water, it may break the bonds that hold the water molecule together, producing fragments such as hydrogen (H) and hydroxyls (OH). These fragments may recombine or may interact with other fragments or ions to form compounds, such as water, which would not harm the cell. However, they could combine to form toxic substances, such as hydrogen peroxide (H2O2), which can contribute to the destruction of the cell.

Radiation
Ionizing radiation is energy transmitted via X rays, gamma rays, beta particles (high speed electrons), alpha particles (the nucleus of the helium atom), neutrons, protons, and other heavy ions such as the nuclei of argon, nitrogen, carbon, and other elements. X rays and gamma rays are electromagnetic waves like light, but their energy is much higher than that of light (their wavelengths are much shorter). Ultraviolet (UV) light is a radiation of intermediate energy that can damage cells (the well known sunburn), but UV light differs from the forms of electromagnetic radiation mentioned above in that it does not cause ionization (loss of an electron) in atoms or molecules, but rather excitation (change in
3

energy level of an electron). The other forms of radiation--particles--are either negatively charged (electrons), positively charged (protons, alpha rays, and other heavy ions), or electrically neutral (neutrons).

Ionization
In contrast, when an electron passes through a cell, it releases its energy along its path (called a track) by interacting with the electrons of nearby molecules. The released energy is absorbed by atoms near the track, resulting in either excitation (a shift in the orbit of an electron to a higher energy level) or ionization (release of an electron from the atom). What differs from an ordinary chemical reaction is that when radiation donates energy to atoms or molecules, electrons other than those on the most outer orbit can be released, which makes the atoms very unstable. Such unstable atoms are called radicals and are chemically very reactive. Some radicals are so reactive that they exist only for as short a time as a microsecond. X and gamma rays differ from beta particles in that they release high-speed electrons from atoms first. Positively charged particles transfer energy to molecules in cells by essentially the same mechanisms. Neutrons are somewhat different since they are electrically uncharged, and their main effect is to impact the nuclei of hydrogen atoms, namely protons. Since the masses of a neutron and a proton are similar, the impact results in an elastic scattering process like in billiards. The ejected protons behave as charged particles.

How ionizations affect cells

Radiation-induced ionizations may act directly on the cellular component molecules or indirectly on water molecules, causing water-derived radicals. Radicals react with nearby molecules in a very short time, resulting in breakage of chemical bonds or oxidation (addition of oxygen atoms) of the affected molecules. The major effect in cells is DNA breaks. Since DNA consists of a pair of complementary double strands, breaks of either a single strand or both strands can occur. However, the latter is believed to be much more important biologically. Most single-strand breaks can be repaired normally thanks to the double-stranded nature of the DNA molecule (the two strands complement each other, so that an intact strand can serve as a template for repair of its damaged, opposite strand). In the case of double-strand breaks, however, repair is more difficult and erroneous rejoining of broken ends may occur. These socalled misrepairs result in induction of mutations, chromosome aberrations, or cell death.

Characteristics of DNA damage by radiation exposure

Deletion of DNA segments is the predominant form of radiation damage in cells that survive irradiation. It may be caused by (1) misrepair of two separate double-strand breaks in a DNA molecule with joining of the two outer ends and loss of the fragment between the breaks or (2) the process of cleaning (enzyme digestion of nucleotides--the component molecules of DNA) of the broken ends before rejoining to repair one doublestrand break.

Biological effects differ by type of radiation

Radiations differ not only by their constituents (electrons, protons, neutrons, etc.) but also by their energy. Radiations that cause dense ionization along their track (such as neutrons) are called high-linear-energy-transfer (high-LET) radiation, a physical parameter to describe average energy released per unit length of the track. (See the accompanying figure.) Low-LET radiations produce ionizations only sparsely along their track and, hence, almost homogeneously within a cell. Radiation dose is the amount of energy per unit of biological material (e.g., number of ionizations per cell). Thus, high-LET radiations are more destructive to biological material than low-LET radiations--such as X and gamma rays--because at the same dose, the low-LET radiations induce the same number of radicals more sparsely within a cell, whereas the high-LET radiations--such as neutrons and alpha particles--transfer most of their energy to a small region of the cell.

Which cells are sensitive to radiation

Not all living cells are equally sensitive to radiation. Those cells which are actively reproducing are more sensitive than those which are not. This is because dividing cells require correct DNA information in order for the cells offspring to survive. A direct interaction of radiation with an active cell could result in the death or mutation of the cell, whereas a direct interaction with the DNA of a dormant cell would have less of an effect. As a result, living cells can be classified according to their rate of reproduction, which also indicates their relative sensitivity to radiation. This means that different cell systems have different sensitivities. Lymphocytes (white blood cells) and cells which produce blood are constantly regenerating, and are, therefore, the most sensitive. Reproductive and gastrointestinal cells are not regenerating as quickly and are less sensitive. The nerve and muscle cells are the slowest to regenerate and are the least sensitive cells. Cells, like the human body, have a tremendous ability to repair damage. As a result, not all radiation effects are irreversible. In many instances, the cells are able to completely repair any damage and function normally. If the damage is severe enough, the affected cell dies. In some instances, the cell is damaged but is still able to reproduce. The daughter cells, however, may be lacking in some critical life sustaining component, and they die. The other possible result of radiation exposure is that the cell is affected in such a way that it does not die but is simply mutated. The mutated cell reproduces and thus perpetuates the mutation. This could be the beginning of a malignant tumour.

Organs sensitive to radiation

The sensitivity of the various organs of the human body correlate with the relative sensitivity of the cells from which they are composed. For example, since the blood forming cells were one of the most sensitive cells due to their rapid regeneration rate, the blood forming organs are one of the most sensitive organs to radiation. Muscle and nerve cells were relatively insensitive to radiation, and therefore, so are the muscles and the brain.

Effect of radiations on cells

The radiations damage the cells in many ways and some of them are listed below: 1. 2. 3. 4. 5. 6. It affects the RBC, WBC and platelets. Taking doses of radiation over a period of time leads to anaemia. It also leads to haemorrhage. The radiations affect the intestine. Exposure to high doses of radiation leads to leukaemia. Also being exposed to radiation over a period of time leads to eye cataract, premature aging, and reduced life time of individual.

Effect of radiations on tumour

The rate of reproduction of the cells forming an organ system is not the only criterion for determining overall sensitivity. The relative importance of the organ system to the well being of the body is also important.

One example of a very sensitive cell system is a malignant tumour. The outer layer of cells reproduces rapidly, and also has a good supply of blood and oxygen. Cells are most sensitive when they are reproducing, and the presence of oxygen increases sensitivity to radiation. Anoxic cells (cells with insufficient oxygen) tend to be inactive, such as the cells located in the interior of a tumour. As the tumour is exposed to radiation, the outer layer of rapidly dividing cells is destroyed, causing it to shrink in size. If the tumour is given a massive dose to destroy it completely, the patient might die as well. Instead, the tumour is given a small dose each day, which gives the healthy tissue a chance to recover from any damage while gradually shrinking the highly sensitive tumour. Another cell system that is composed of rapidly dividing cells with a good blood supply and lots of oxygen is the developing embryo. Therefore, the sensitivity of the developing embryo to radiation exposure is similar to that of the tumour; however, the consequences are dramatically different. There are various factors on which the sensitivity of radiations depends. They are: 1. 2. 3. 4. 5. 6. Total Dose Type of Cell Type of Radiation Age of Individual Stage of Cell Division Part of Body Exposed
7

7. General State of Health 8. Tissue Volume Exposed Time 9. Interval over which Dose is Received

Whole body sensitivity depends upon the most sensitive organs which, in turn, depend upon the most sensitive cells. As noted previously, the most sensitive organs are the blood forming organs and the gastrointestinal system. The biological effects on the whole body from exposure to radiation will depend upon several factors. Some of these are listed above. For example, a person, already susceptible to infection, who receives a large dose of radiation, may be affected by the radiation more than a healthy person.

Radiation effect can be divided into two parts mainly 1. Low doses (chronic) 2. High doses (acute) Biological effects of radiation are typically divided into two categories. The first category consists of exposure to high doses of radiation over short periods of time producing acute or short term effects. The second category represents exposure to low doses of radiation over an extended period of time producing chronic or long term effects. High doses tend to kill cells, while low doses tend to damage or change them. High doses can kill so many cells that tissues and organs are damaged.

High dose effects

A number of high dose effects have been described. Other high dose effect includes skin burns, hair loss, sterility and cataract. Besides death, there are several other possible effects of a high radiation dose.

S.No
1. 2. 3. 4. 5. 6.

Dose ( rad )
15-25 50 100 150 320-360 480-540

Effect observed
Blood count changes in a group of people Blood count changes in an individual Vomiting Death With medical care With supportive care medical
8

Effects on the skin include erythema (reddening like sunburn), dry desquamation (peeling), and moist desquamation (blistering). Skin effects are more likely to occur with exposure to low energy gamma, X-ray, or beta radiation. Most of the energy of the radiation is deposited in the skin surface. The dose required for erythema to occur is relatively high, in excess of 300 rad. Blistering requires a dose in excess of 1,200 rad. Hair loss, also called epilation, is similar to skin effects and can occur after acute doses of about 500 rad. Sterility can be temporary or permanent in males, depending upon the dose. In females, it is usually permanent, but it requires a higher dose. To produce permanent sterility, a dose in excess of 400 rad is required to the reproductive organs. Cataracts (a clouding of the lens of the eye) appear to have a threshold of about 200 rad. Neutrons are especially effective in producing cataracts, because the eye has a high water content, which is particularly effective in stopping neutrons.

Low Dose Effects

There are three general categories of effects resulting from exposure to low doses of radiation. These are: Genetic - The effect is suffered by the offspring of the individual exposed. Somatic - The effect is primarily suffered by the individual exposed. Since cancer is the primary result, it is sometimes called the Carcinogenic Effect. In-Utero - Some mistakenly consider this to be a genetic consequence of radiation exposure because the effect, suffered by a developing embryo/foetus, is seen after birth. However, this is actually a special case of the somatic effect, since the embryo/foetus is the one exposed to the radiation.

Genetic Effects
Mutation of the reproductive cells passed on to the offspring of the exposed individual. The Genetic Effect involves the mutation of very specific cells, namely the sperm or egg cells. Mutations of these reproductive cells are passed to the offspring of the individual exposed. Radiation is an example of a physical mutagenic agent. There are also many chemical agents as well as biological agents (such as viruses) that cause mutations. One very important fact to remember is that radiation increases the spontaneous mutation rate, but does not produce any new mutations. Therefore, despite all of the hideous creatures supposedly produced by radiation in the science fiction literature and
9

cinema, no such transformations have been observed in humans. One possible reason why genetic effects from low dose exposures have not been observed in human studies is that mutations in the reproductive cells may produce such significant changes in the fertilized egg that the result is a nonviable organism which is spontaneously resorbed or aborted during the earliest stages of fertilization. Although not all mutations would be lethal or even harmful, it is prudent to assume that all mutations are bad, and thus, by USNRC regulation (10 CFR Part 20), radiation exposure shall be held to the absolute minimum or As Low as Reasonably Achievable (ALARA). This is particularly important since it is believed that risk is directly proportional to dose, without any threshold.

Somatic Effects
Effect is suffered by the individual exposed. Primary consequence is cancer. Somatic effects (carcinogenic) are, from an occupational risk perspective, the most significant since the individual exposed (usually the radiation worker) suffers the consequences (typically cancer). As noted in the USNRC Regulatory Guide 8.29, this is also the NRCs greatest concern. Radiation is an example of a physical carcinogenic, while cigarettes are an example of a chemical cancer causing agent. Viruses are examples of biological carcinogenic agents. Unlike genetic effects of radiation, radiation induced cancer is well documented. Many studies have been completed which directly link the induction of cancer and exposure to radiation.

Some of the population studied and their associated cancers are:

Lung cancer - uranium miners Bone cancer - radium dial painters Thyroid cancer - therapy patients Breast cancer - therapy patients Skin cancer - radiologists Leukaemia - bomb survivors, in-utero exposures, radiologists, therapy patients

10

In-Utero Effects
This basically involves: Effects of radiation on embryo/foetus Intrauterine Death Growth Retardation Developmental Abnormalities Childhood Cancers

The in-utero effect involves the production of malformations in developing embryos. Radiation is a physical teratogenic agent. There are many chemical agents (such as thalidomide) and many biological agents (such as the viruses which cause German measles) that can also produce malformations while the baby is still in the embryonic or foetal stage of development. The effects from in-utero exposure can be considered a subset of the general category of somatic effects. The malformation produced does not indicate a genetic effect since it is the embryo that is exposed, not the reproductive cells of the parents.

Radiation Risk
With any exposure to radiation, there is some risk which can be divided for genetic, somatic and in utero effect. Genetic - Risks from 1 rem (Roentgen equivalent man) of radiation exposure to the reproductive organs are approximately 50 to 1,000 times less than the spontaneous risk for various anomalies. Somatic - For radiation induced cancers, the risk estimate is small compared to the normal Incidence of about 1 in 4 chances of developing any type of cancer. However, not all cancers are associated with exposure to radiation. The risk of dying from radiation induced cancer is about one half the risk of getting the cancer. In-Utero - Spontaneous risks of foetal abnormalities are about 5 to 30 times greater than the risk of exposure to 1 rem of radiation. However, the risk of childhood cancer from exposure in-utero is about the same as the risk to adults exposed to radiation. By far, medical practice is the largest source of in-utero radiation exposure. A graph showing the relationship between dose of the radiation in rad and the risk associated with it is shown below:

11

General consensus among experts is that some radiation risks are related to radiation dose by a linear, no-threshold model. This model is accepted by the NRC since it appears to be the most conservative.

Effects of Radiation on the Human Body

12

(1) Hair The losing of hair quickly and in clumps occurs with radiation exposure at 200 rems or higher. (2) Brain Since brain cells do not reproduce, they won't be damaged directly unless the exposure is 5,000 rems or greater. Like the heart, radiation kills nerve cells and small blood vessels, and can cause seizures and immediate death. (3) Thyroid The certain body parts are more specifically affected by exposure to different types of radiation sources. The thyroid gland is susceptible to radioactive iodine. In sufficient amounts, radioactive iodine can destroy all or part of the thyroid. By taking potassium iodide, one can reduce the effects of exposure. (4) Blood System When a person is exposed to around 100 rems, the blood's lymphocyte cell count will be reduced, leaving the victim more susceptible to infection. This is often referred to as mild radiation sickness. Early symptoms of radiation sickness mimic those of flu and may go unnoticed unless a blood count is done. According to data from Hiroshima and Nagasaki, show that symptoms may persist for up to 10 years and may also have an increased longterm risk for leukaemia and lymphoma. (5) Heart Intense exposure to radioactive material at 1,000 to 5,000 rems would do immediate damage to small blood vessels and probably cause heart failure and death directly. (6) Gastrointestinal Tract Radiation damage to the intestinal tract lining will cause nausea, bloody vomiting and diarrhoea. This is occurs when the victim's exposure is 200 rems or more. The radiation will begin to destroy the cells in the body that divide rapidly. These including blood, GI tract, reproductive and hair cells, and harm their DNA and RNA of surviving cells. (7) Reproductive Tract

Because reproductive tract cells divide rapidly, these areas of the body can be damaged at rem levels as low as 200. Long-term, some radiation sickness victims will become sterile.

13

Radiation Therapy
Radiation therapy (in American English), radiation oncology, or radiotherapy (in the UK, Canada and Australia), sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control or kill malignant cells. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. It may also be used as part of curative therapy, to prevent tumour recurrence after surgery to remove a primary malignant tumour (for example, early stages of breast cancer). Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. Radiation therapy is commonly applied to the cancerous tumour because of its ability to control cell growth. Ionizing radiation works by damaging the DNA of exposed tissue leading to cellular death. To spare normal tissues (such as skin or organs which radiation must pass through to treat the tumour), shaped radiation beams are aimed from several angles of exposure to intersect at the tumour, providing a much larger absorbed dose there than in the surrounding, healthy tissue. Besides the tumour itself, the radiation fields may also include the draining lymph nodes if they are clinically or radio logically involved with tumour, or if there is thought to be a risk of subclinical malignant spread. It is necessary to include a margin of normal tissue around the tumour to allow for uncertainties in daily set-up and internal tumour motion. These uncertainties can be caused by internal movement (for example, respiration and bladder filling) and movement of external skin marks relative to the tumour position. Radiation oncology is the medical specialty concerned with prescribing radiation, and is distinct from radiology, the use of radiation in medical imaging and diagnosis. Radiation may be prescribed by a radiation oncologist with intent to cure ("curative") or for adjuvant therapy. It may also be used as palliative treatment (where cure is not possible and the aim is for local disease control or symptomatic relief) or as therapeutic treatment (where the therapy has survival benefit and it can be curative). It is also common to combine radiation therapy with surgery, chemotherapy, hormone therapy, immunotherapy or some mixture of the four. Most common cancer types can be treated with radiation therapy in some way. The precise treatment intent (curative, adjuvant, neoadjuvant, therapeutic, or palliative) will depend on the tumour type, location, and stage, as well as the general health of the patient. Total body irradiation (TBI) is a radiation therapy technique used to prepare the body to receive a bone marrow transplant. Brachytherapy, in which a radiation source is placed inside or next to the area requiring treatment, is another form of radiation therapy that minimizes exposure to healthy tissue during procedures to treat cancers of the breast, prostate and other organs. Radiation therapy has several applications in non-malignant conditions, such as the treatment of trigeminal neuralgia, acoustic neuromas, severe thyroid eye disease, pterygium, pigmented villonodular synovitis, and prevention of keloid scar growth, vascular restenosis, and heterotopic ossification. The use of radiation therapy in non-malignant conditions is limited partly by worries about the risk of radiation-induced cancers.
14

Mechanism of action
Radiation therapy works by damaging the DNA of cancerous cells. This DNA damage is caused by one of two types of energy, photon or charged particle. This damage is either direct or indirect ionization of the atoms which make up the DNA chain. Indirect ionization happens as a result of the ionization of water, forming free radicals, notably hydroxyl radicals, which then damage the DNA. In photon therapy, most of the radiation effect is through free radicals. Because cells have mechanisms for repairing single-strand DNA damage, double-stranded DNA breaks prove to be the most significant technique to cause cell death. Cancer cells are generally undifferentiated and stem cell-like; they reproduce more than most healthy differentiated cells, and have a diminished ability to repair sub-lethal damage. Single-strand DNA damage is then passed on through cell division; damage to the cancer cells' DNA accumulates, causing them to die or reproduce more slowly. One of the major limitations of photon radiation therapy is that the cells of solid tumours become deficient in oxygen. Solid tumours can outgrow their blood supply, causing a lowoxygen state known as hypoxia. Oxygen is a potent radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals.

Tumour cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in a normal oxygen environment. Much research has been devoted to overcoming hypoxia including the use of high pressure oxygen tanks, blood substitutes that carry increased oxygen, hypoxic cell radiosensitizer drugs such as misonidazole and metronidazole, and hypoxic cytotoxins (tissue poisons), such as tirapazamine. Newer research approaches are currently being studied, including preclinical and clinical investigations into the use of an oxygen diffusion-enhancing compound such as trans sodium crocetinate (TSC) as a radiosensitizer. Charged particles such as proton, boron, carbon, and neon ions can cause direct damage to cancer cell DNA through high-LET (linear energy transfer) and have an antitumour effect independent of tumour oxygen supply because these particles act mostly via direct energy transfer usually causing double-stranded DNA breaks. Due to their relatively large mass, protons and other charged particles have little lateral side scatter in the tissue the beam does not broaden much, stays focused on the tumour shape, and delivers small dose sideeffects to surrounding tissue. They also more precisely target the tumour using the Bragg peak effect. See proton therapy for a good example of the different effects of IMRT vs. charged particle therapy. This procedure reduces damage to healthy tissue between the charged particle radiation source and the tumour and sets a finite range for tissue damage after the tumour has been reached. In contrast, IMRT's use of uncharged particles causes its energy to damage healthy cells when it exits the body. This exiting damage is not therapeutic, can increase treatment side effects, and increases the probability of secondary cancer induction.[3] This difference is very important in cases where the close proximity of other organs makes any stray ionization very damaging (example: head and neck cancers).
15

This x-ray exposure is especially bad for children, due to their growing bodies, and they have a 30% chance of a second malignancy after 5 years post initial RT.[4]

Dose
The amount of radiation used in photon radiation therapy is measured in gray (Gy), and varies depending on the type and stage of cancer being treated. For curative cases, the typical dose for a solid epithelial tumour ranges from 60 to 80 Gy, while lymphomas are treated with 20 to 40 Gy. Preventative (adjuvant) doses are typically around 45 60 Gy in 1.8 2 Gy fractions (for breast, head, and neck cancers.) Many other factors are considered by radiation oncologists when selecting a dose, including whether the patient is receiving chemotherapy, patient comorbidities, whether radiation therapy is being administered before or after surgery, and the degree of success of surgery. Delivery parameters of a prescribed dose are determined during treatment planning (part of dosimetry). Treatment planning is generally performed on dedicated computers using specialized treatment planning software. Depending on the radiation delivery method, several angles or sources may be used to sum to the total necessary dose. The planner will try to design a plan that delivers a uniform prescription dose to the tumour and minimizes dose to surrounding healthy tissues.

Fractionation
(This section only applies to photon RT although other types of radiation therapy may be fractionated). The total dose is fractionated (spread out over time) for several important reasons. Fractionation allows normal cells time to recover, while tumour cells are generally less efficient in repair between fractions. Fractionation also allows tumour cells that were in a relatively radio-resistant phase of the cell cycle during one treatment to cycle into a sensitive phase of the cycle before the next fraction is given. Similarly, tumour cells that were chronically or acutely hypoxic (and therefore more radioresistant) may reoxygenate between fractions, improving the tumour cell kill. Fractionation regimens are individualised between different radiation therapy centers and even between individual doctors. In North America, Australia, and Europe, the typical fractionation schedule for adults is 1.8 to 2 Gy per day, five days a week. In some cancer types, prolongation of the fraction schedule over too long can allow for the tumour to begin repopulating, and for these tumour types, including head-and-neck and cervical squamous cell cancers, radiation treatment is preferably completed within a certain amount of time. For children, a typical fraction size may be 1.5 to 1.8 Gy per day, as smaller fraction sizes are associated with reduced incidence and severity of late-onset side effects in normal tissues.

16

In some cases, two fractions per day are used near the end of a course of treatment. This schedule, known as a concomitant boost regimen or hyper fractionation, is used on tumours that regenerate more quickly when they are smaller. In particular, tumours in the head-andneck demonstrate this behaviour. One fractionation schedule that is currently being heavily studied is hypo fractionation. This is a radiation treatment in which the total dose of radiation is divided into large doses, and treatments are given less than once a day. Typical doses vary significantly by cancer type, from 3Gy/fraction to 20Gy/fraction. The logic behind hypo fractionation is to lessen the possibility of the cancer returning by not giving the cells enough time to reproduce. One of the best-known alternative fractionation schedules is Continuous Hyper fractionated Accelerated Radiation therapy (CHART). CHART, used to treat lung cancer, consists of three smaller fractions per day. Although reasonably successful, CHART can be a strain on radiation therapy departments. Another increasingly well-known alternative fractionation schedule, used to treat breast cancer, is called Accelerated Partial Breast Irradiation (APBI). APBI can be performed with either brachytherapy or with external beam radiation. APBI normally involves two high-dose fractions per day for five days, compared to whole breast irradiation, in which a single, smaller fraction is given five times a week over a six-to-seven-week period. Implants can be fractionated over minutes or hours, or they can be permanent seeds which slowly deliver radiation until they become inactive.

Effect on different types of cancer

Different cancers respond differently to radiation therapy. The response of a cancer to radiation is described by its radiosensitivity. Highly radiosensitive cancer cells are rapidly killed by modest doses of radiation. These include leukemias, most lymphomas and germ cell tumours. The majority of epithelial cancers are only moderately radiosensitive, and require a significantly higher dose of radiation (6070Gy) to achieve a radical cure. Some types of cancer are notably radioresistant, that is, much higher doses are required to produce a radical cure than may be safe in clinical practice. Renal cell cancer and melanoma are generally considered to be radioresistant. It is important to distinguish the radiosensitivity of a particular tumour, which to some extent is a laboratory measure, from the radiation "curability" of a cancer in actual clinical practice. For example, leukemias are not generally curable with radiation therapy, because they are disseminated through the body. Lymphoma may be radically curable if it is localised to one area of the body. Similarly, many of the common, moderately radioresponsive tumours are routinely treated with curative doses of radiation therapy if they are at an early stage. For example: non-melanoma skin cancer, head and neck cancer, breast cancer, non17

small cell lung cancer, cervical cancer, anal cancer, prostate cancer. Metastatic cancers are generally incurable with radiation therapy because it is not possible to treat the whole body. Before treatment, a CT scan is often performed to identify the tumour and surrounding normal structures. The patient is then sent for a simulation so that molds can be created to be used during treatment. The patient receives small skin marks to guide the placement of treatment fields. The response of a tumour to radiation therapy is also related to its size. For complex reasons, very large tumours respond less well to radiation than smaller tumours or microscopic disease. Various strategies are used to overcome this effect. The most common technique is surgical resection prior to radiation therapy. This is most commonly seen in the treatment of breast cancer with wide local excision or mastectomy followed by adjuvant radiation therapy. Another method is to shrink the tumour with neoadjuvant chemotherapy prior to radical radiation therapy. A third technique is to enhance the radiosensitivity of the cancer by giving certain drugs during a course of radiation therapy. Examples of radiosensiting drugs include: Cisplatin, Nimorazole, and Cetuximab.

Types
Historically, the three main divisions of radiation therapy are external beam radiation therapy (EBRT or XRT) or teletherapy, brachytherapy or sealed source radiation therapy, and systemic radioisotope therapy or unsealed source radiotherapy. The differences relate to the position of the radiation source; external is outside the body, brachytherapy uses sealed radioactive sources placed precisely in the area under treatment, and systemic radioisotopes are given by infusion or oral ingestion. Brachytherapy can use temporary or permanent placement of radioactive sources. The temporary sources are usually placed by a technique called afterloading. In afterloading a hollow tube or applicator is placed surgically in the organ to be treated, and the sources are loaded into the applicator after the applicator is implanted. This minimizes radiation exposure to health care personnel. Particle therapy is a special case of external beam radiation therapy where the particles are protons or heavier ions. Intraoperative radiation therapy or IORT is a special type of radiation therapy that is delivered immediately after surgical removal of the cancer. This method has been employed in breast cancer (TARGeted Introperative radiation therapy or TARGIT), brain tumours and rectal cancers.

18

Bibliography
Fundamental Concepts of Environmental Chemistry by G.S.Sodhi. Alpha Science International, Ltd; 1 edition (August 1, 2000) Atomicarchive.com (http://www.atomicarchive.com/Effects/radeffects.shtml#Hair) Date accessed on: 20/02/2013 Radiation effects Research Foundation http://www.rerf.jp/radefx/basickno_e/radcell.htm Date accessed on: 02/02/2013

19