Radiation Biology


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Radiation Biology

  1. 1. By Dr. Hassan M. Abouelkheir BDS, Msc, PhD.
  2. 2. ! ! ! Linear: the response is directly related to the dose. ! Non-linear: the response is not proportionate to the dose. linear ! Threshold: the dose at which effects non-linear are produced; below this dose, there are no obvious effects. Dose ! Non-threshold: any dose produces a threshold non-threshold response. Response !
  3. 3. ! ! Stochastic effect: occurs by chance, usually without a threshold level of dose. The probability of a stochastic effect is increased with increasing doses, but the severity of the response is not proportional to the dose. Genetic mutations and cancer are the two main stochastic effects. Deterministic effect: health effects that increase in severity with increasing dose above a threshold level. Usually associated with a relatively high dose delivered over a short period of time. Skin erythema (reddening) and cataract formation from radiation are two examples of deterministic effects.
  4. 4. DNA Radiation effects at the cellular level result from changes in a critical or “target” molecule. This target molecule is DNA (deoxyribonucleic acid), which regulates cellular activity and contains genetic information needed for cell replication. The DNA molecule is called a chromosome. Permanent changes in this molecule will alter cell function and may result in cell death.
  5. 5. Direct vs. Indirect Effect If an x-ray or some type of particulate radiation interacts with the DNA molecule, this is considered a direct effect. Particulate radiation, because of its mass, is more apt to cause damage to the DNA by this direct effect. Other molecules that contribute to cell function, such as RNA, proteins, and enzymes, may also be affected by the direct effect. DNA x-ray or particulate radiation = Direct effect
  6. 6. Direct vs. Indirect Effect Most of the damage to DNA molecules from x-rays is accomplished through the indirect effect. When x-rays enter a cell, they are much more likely to hit a water molecule because there are a large number of water molecules in each cell. When the x-ray ionizes the water molecule, ions and free radicals are produced which in turn bond with a DNA molecule, changing its structure. Since the x-ray interacted with the water molecule before the DNA was involved, this is considered an indirect effect. H2O x-ray or particulate radiation ions and free radicals DNA Indirect = effect
  7. 7. Free Radical A free radical is an atom or molecule that has an unpaired electron in the valence shell, making it highly reactive. These free radicals aggressively join with the DNA molecule to produce damage. In the presence of oxygen, the hydroperoxyl free radical is formed; this is one of the most damaging free radicals that can be produced. Free radicals are the primary mediator of the indirect effects on DNA.
  8. 8. ! ! ! Radiolysis of water: As a result of the living body consists of 70- 90% water . So ionization of pure water leads to fast moving free electron : and +ve charged molecule. Both peroxyl radicals and hydrogen peroxide are oxidizing agents that alter biological molecules and cause cell destruction.
  9. 9. ! DNA is more radiosensitive than RNA. ! 1. Change or loss of base. 2. Disruption of hydrogen bonds between DNA strands. 3. Breakage of one or both DNA strands. 4. Cross-linkage of DNA strands within the helix to other DNA or proteins. ! ! !
  10. 10. ! ! ! ! Cells undamaged: ionization alters the structure of the cells but has no overall negative effect. ! Sublethal injury: cells are damaged by ionization but the damage is repaired. ! Mutation: cell injury may be incorrectly repaired, and cell function is altered or the cell may reproduce at an uncontrolled rate (cancer). ! Cell death: the cell damage is so extensive that the cell is no longer able to reproduce.
  11. 11. Sublethal Injury: Cellular Repair 1. Ionization causes damage to DNA (single-strand break of DNA). ! 2. Cellular enzymes recognize the damage and coordinate the removal of the damaged section. ! 3. Additional cell enzymes organize replacement of the damaged section with new material.
  12. 12. Cell Cycle More damage results when the cell is irradiated during the G1/early S portion of the cell cycle (before DNA synthesis); the damaged DNA (chromosome) will be duplicated during DNA synthesis and will result in a break in both arms of the chromosome at the next mitosis. G1 = gap phase 1 in which nuclear components are replicated S = synthesis phase; DNA is synthesized during the last 2/3 of this phase G2 = gap phase 2, a preparatory stage to cell division M = mitosis, during which cells divide Cell most sensitive to radiation
  13. 13. Radiosensitive Cells Cells that are more easily damaged by radiation are radiosensitive. The characteristics of radiosensitive cells are: 1. High reproductive rate (many mitoses) 2. Undifferentiated (immature) 3. High metabolic rate Lymphocytes, germ cells, basal cells of skin and mucosa, and erythroblasts are examples of radiosensitive cells.
  14. 14. Radioresistant Cells Cells that are not as susceptible to damage from radiation are radioresistant. The characteristics of radioresistant cells are: 1. Low reproductive rate (few mitoses) 2. Well differentiated (mature) 3. Low metabolic rate Nerve and muscle cells are examples of radioresistant cells.
  15. 15. ! ! ! ! Nucleus: It causes inhibition of cell division. cytoplasm: It causes increased permeability to potassium and Na- ions and changes in active transport mechanisms. Nucleus is more sensitive than cytoplasm. The sensitive site in the nucleus is DNA within chromosomes. Chromosome Aberrations: are observed when DNA condenses to form chromosomes at the time of mitosis.
  16. 16. ! ! ! Irradiation to rapidly dividing cells such as hematopoietic tissues causes reduction in the size of the irradiated tissue as a result of mitotic delay and cell death.(usually during mitosis). 3 mechanisms are responsible for reproductive death: 1- DNA Damage: causes chromosomal aberrations cell death after few mitosis from irradiation.
  17. 17. ! ! ! ! ! 2- Bystander Effect: Irradiated cells damaged by release molecules that kill nearby cells . This bystander effect occur upon irradiation by α particles & x-rays . This causes cell killing, gene mutations and carcinogens. 3- Apoptosis: a programmed cell death without necrosis . Cells round up, draw away from their neighbors and condense nuclear chromatin. Recovery: cell recovery from DNA damage and by stander effect involves enzymatic repair of single – strand breaks of DNA. Specially multiple infractionated dose .
  18. 18. ! ! ! ! Radiosensitivity of a tissue or organ is measured by its response to irradiation. Small number of lost cells--> no clinical effect. Large no. of lost cells-->clinical effect. The dose + amount of cell loss ->deterministic effect.
  19. 19. ! Effects seen in first days or weeks are determined by sensitivity of tissue parenchymal cells. High radiosentive cells as bone marrow or mucous membrane effects can be seen quickly. Rather than relativily radiosensitive cells as muscles.
  20. 20. ! ! ! Effects that seen after months or years from exposure are loss of parenchymal cells and replaced by fibrous connective tissue. It is caused by death of replicating cells and bt damage to the fine vasculature. Both radiosensitive and radioresistant parenchymal cells will be replaced by fibrous connective tissue.
  21. 21. ! The biological response to radiation is dependent on several different factors. These include: ! 1- Total Dose: the higher the radiation dose, the greater the potential cellular damage. ! 2- Dose Rate: A high dose given over a short period of time (or all at once) will produce more damage than the same dose received over a longer period of time.
  22. 22. 3- Oxygen Effect: Radiation effects are more pronounced in the presence of oxygen. Oxygen is required for the formation of the hydroperoxyl free radical, which is the most damaging free radical formed following ionization. 4-Linear Energy Transfer: This measures the rate of the loss of energy as radiation moves through tissue. Particulate radiation (alpha particles, electrons, etc.) has a higher LET because it has mass and interacts with tissues much more readily than do x-rays.
  23. 23. ! ! Treating radiosensitive oral malignant tumors depends on many factors such as radiosensitivity , histology, size, location, invasion into adjacent structures and duration of symptomatology. Fractionation of total x-ray dose into multiple small doses is better to increase cellular repair and O2 tension in irradiated tumor make it more radiosensitive.
  24. 24. A- Oral mucous membrane: 1. Redness and inflammation of mm(mucositis). 2. White to yellow pseudomembrane. 3. At the end of therapy sever discomfort and difficulty to eat. 4. Dry infection with candida albicans. 5-Healing within 2 months.
  25. 25. ! ! ! ! They are sensitive to radiotherapy. Patient feels loss of taste during 2nd or 3rd week of radiotherapy. Irradiation to posterior 21/3 of tongue affect bitter and acid flavors while anterior 1/3 affect sweet and salt flavors. Recovery takes about 60 to 120 days after irradiation.
  26. 26. ! ! ! The parotid salivary glands are more radiosensitve rather than submand/lingual. Acute inflammatory response soon develop. Chronic inflammatory progression leads to progressive fibrosis, adiposis, loss of fine vasculature and degeneration
  27. 27. ! ! After few weeks of radiotherapy ,salivary flow decrease to zero at 60 Gray. Dryness of mouth usually subsides in 6 to 12 months because of cmpensatory hypertrophy of residual salivary gland tissues. ! ! Xerostomia beyond a year is less likely to show significant return of function.
  28. 28. ! ! ! Irradiation of teeth during their development retards their growth. If it precedes calcification it may destroy tooth bud . After calcification it may inhibit cellular differentiation causing malformation and arresting general growth. Children receiving radiation therapy shows defects in permanent dentition such as retarded root development or missing 1 or 2.
  29. 29. It is a rampant form of dental decay result from radiotherapy of salivary glands leading to xerostomia which causes caries due to: a. Reduced salivary flow. B. Decreased pH. C. Reduced buffering capacity. D. Increased viscosity. !
  30. 30. ! ! ! ! 3 types of radiation caries; 1. Wide spread superficial lesions attacking buccal, occlusal , incisal and palatal surfaces(most common). 2. Cirumferentially cervically involving dentine and cementum. 3. Dark pigmentation of entire crown and incisor edges may be worn.
  31. 31. A. Daily application of 1% Na F gel topically. B) Reduce streptococcus mutans & Lactobacillus. C. Oral hygiene instructions. D. Restorative dental procedures.
  32. 32. ! ! The primary damage of mature bone due to damage of fine vasculature specially in mandible rather than maxilla. The marrow tissue becomes hypovascular, hypo toxic and hypo cellular with replacement of normal marrow with fatty marrow of fibrous C.T.
  33. 33. ! In non-healing wound as result of extraction wound or denture sore breaking of mm leading to infection and necrosis of bone so called Osteoradionecrosis.
  34. 34. ! ! ! It is recommended to do extraction & alveolectomies 2 to 3 weeks before irradiation . This allow time for healing. Post-irradiation extractions must be accompanied with alveolectomy to protect mucosa from trauma of prosthetic appliance and preferred with hyperbaric oxygen.
  35. 35. Acute Radiation syndrome: ! it is a collection of the signs and symptoms as a result of radiotherapy, atom bomb blasts and radiation accidents. ! It ranges from prodromal symptoms to hematopoietic, gastrointestinal, cardiovascular & CNS symptoms.
  36. 36. ! ! Embryonic cell are highly radiosensitive as they relatively undifferentiated and rapidly mitotic. During periods of implantation [10-14] days after conception in humans embryo may show malformation.
  37. 37. ! ! Organogenesis period [18-45 of gestation] is the most sensitive period . It causes growth retardation , microcephaly and mental retardation.
  38. 38. Carcinogenesis: 1. Most cancer appear 10 years after exposure. 2. Childhood risk exposure is twice as large as adulthood risk. 3. The mortality rate show no linearity below 4SV. 4.Cancer due to radiation is multiple of spontaneous rate.
  39. 39. ! ! Incidence of leukemia rises following exposure to radiation from 5-30 years. Children under 20 are more at risk than adults.
  40. 40. ! ! ! Dental radiographic examination carries certainly small risk. This could be reduced by using E-speed film and rectangular collimators. The highest estimated risk from leukemia & for thyroid & bone surface cancers. The panoramic radiography carries one tenth the risk of full mouth radiogaphy.
  41. 41. ! ! ! ! ! ! Growth and development: Children exposed to bombing showing reduced height, weight & skeletal development. Mental retardation: There is 4% chance of mental retardation per 100 MSV at 8-15 weeks of gestational age. Cataract: The threshold for induction of cataracts ranges from 2-5Gray in single or multiple dose.
  42. 42. ! ! ! Radiation genetic damage may induce new genetic mutation rather than spontaneous mutations in drosophilla. There is no threshold dose below which there is no damage to offspring in human. In humans the genetic doubling dose for mutations resulting in death is approximately 1SV.
  43. 43. Radiation genetics (cont.): ! ! ! In humans the genetic doubling dose for mutations resulting in death is approximately 1SV. The gonadal dose to patients from full mouth radiographic examination is in the range of 2-30µSV. The estimated genetic effects resulting from 10MSV per generation.
  44. 44. THE END THE END