Week 8 a Chapter 33 Radiobiology

1. Week 8 a Chapter 33 Radiobiology • Radiobiology is the study of the effects of ionizing radiation on biologic tissues. • The ultimate goal of research is to develop dose-response relationships so the effects of planned doses can be predicted and the response to accidental exposure better managed.

2. Radiobiology • The effect of x-ray radiation on humans is the result of interactions at the atomic level. • The forms of interaction: • Ionization of the tissue • Excitation of orbital electrons • Results is the disposition of energy in the tissues.

3. Effects of Ionizing Radiation Exposure • When the atom is ionized, its chemical bonding properties change. • If the atom is part of a large molecule, it may result in breakage of the the molecule or relocation of the atom within the molecule. • The abnormal molecule may function improperly or die.

4. Effects of Ionizing Radiation Exposure • This may result in serious impairment of the cell function or cell death. • This process can be reversible if the atom attracts a free electron. • Molecules can be mended by repair enzymes. • Cells and tissue can regenerate.

5. Types of Radiation Response • If the response to radiation happens in minutes or days it is referred to as early effects of radiation. • If the responds is not observed for six months or more, it is termed to be late effects of radiation.

6. Early Responses to Radiation in Humans • Acute radiation syndrome • Hematological Syndrome • Gastrointestinal Syndrome • Central Nervous System Syndrome • Local tissue damage • Skin • Gonads • Extremities

7. Early Responses to Radiation in Humans • Hematological depression • Cytogenesis damage

8. Late Responses to Radiation in Humans • Leukemia • Other malignant disease • Bone Cancer • Lung Cancer • Thyroid Cancer • Breast Cancer

9. Late Responses to Radiation in Humans • Local tissue damage • Skin • Gonads • Eyes • Shortened life span • Genetic damage • Cytogenesis damage • Doubling dose • Genetically significant dose

10. Effects of Fetal Irradiation in Humans • Prenatal death • Neonatal death • Congenital malformations • Childhood malignancy • Diminished growth and development.

11. Effects of Irradiation in Humans • Most of the observed effects have been observed after rather large doses. • As operators of x-ray machines, we must assume that even small doses can be harmful.

12. Population American radiologists Atomic bomb survivors Radiation accident victims Marshall Islanders Uranium miners Radium watch dial painters Patients treated with 131I Children treated for enlarged thymus Irradiation in utero Volunteer convicts Effect Leukemia, reduced life span Malignant disease Acute lethality Thyroid cancer Lung cancer Bone cancer Thyroid cancer Thyroid cancer Childhood malignancy Fertility impairment Human Populations in Which Radiation Effects have Been Observed

13. Sequence of Events after ExposureRadiation

14. Radiation Interaction at the Atomic Level • At the most basic level, the human body is made up of atoms. • Radiation interacts at this level. • The atomic composition of the body determines the character and degree of the radiation interaction. • The molecular and tissue composition defines the nature of the radiation response.

15. Radiation Interaction at the Atomic Level • Over 85% of the body is composed of hydrogen and oxygen. • Radiation interaction at the atomic level results in molecular change, and this in turn can produce a cell deficient in normal growth and metabolism.

16. Molecular Composition • There are five principle types of molecules in the body: • Four are macromolecules , sometimes consisting of hundreds of thousands of atoms. • Proteins • Lipids (fats) • Carbohydrates (sugars and starches) • Nucleic Acids (DNA) • DNA is the most critical & radiosensitive molecule.

17. Molecular Composition • 80% Water • 15% Protein • 2% Lipids • 1% Carbohydrates • 1% Nucleic Acid (DNA) • 1% Other

18. Water 80% • Water is the most abundant and simplest molecule in the body. • It delivers energy to the target molecule and thereby contributing to the radiation affects. • Water also helps control temperature • Water provides form and shape to the cell.

19. Protein 15% • Proteins are long chains of macromolecules consisting of amino acids connected by peptide bonds. • There are 22 amino acids used in protein synthesis or the metabolic production of protein. • The linear sequence determines the function of the protein.

20. Uses of Protein • Proteins provide structure and support. Muscles are very high in protein content. • Proteins function as enzymes, hormones or antibodies.

21. Enzymes • Enzymes are molecules that allow biochemical reactions to continue without being part of the reaction. • They function as a catalyst for the chemical reaction.

22. Hormones & Antibodies • Hormones exercise regulatory control over some body functions such as: • Growth • Development • Metabolic Rate • Hormones produced by the endocrine glands. • Antibodies provide defense from disease.

23. Lipids 2% • Lipids are organic macromolecules composed of carbon, hydrogen and oxygen. • Lipids are composed of glycerol and fatty acids. • Lipids are present in all tissues and are the structural component of cell membranes.

24. Lipids • Lipids tend to concentrate just under the skin. • Lipids provide heat insulation. • Lipids serve as fuel or energy stores for the body. It is more difficult to extract the energy compared to carbohydrates resulting in obesity.

25. Carbohydrates 1% • Like lipids are composed of carbon, hydrogen and oxygen but the structure is different. • The structural difference determines the contribution of the carbohydrate molecule to biochemistry. • Some carbohydrates provide shape and stability to the cell. • Primary function is to provide fuel for cell metabolism.

26. Nucleic Acids 1% • There are two principle nucleic acids of importance to human metabolism. • DNA and RNA • DNA located in the nucleus of the cell serves as the control molecule for cell function. DNA contains all of the heredity information for the cell or the entire organism if it is a germ cell.

27. Nucleic Acids 1% • RNA is found primarily in the cytoplasm but is also found in the nucleus. There are two types of RNA. • Messenger RNA (mRNA) • Transfer RNA (tRNA) • RNA is involved in growth and development of the cell through biochemical pathways, notably through protein synthesis.

28. Nucleic Acids 1% • DNA is the principle radiation sensitive molecule.

29. Human Cell Composition • Two major structure of the cell are: • Nucleus containing the DNA • Cytoplasm makes up the bulk of the cell and contains all of the other cell structures. • Endoplasmic reticulum is a series of channels that allows the nucleus to communicate with the cytoplasm.

30. Human Cell Composition • Mitochondria are large bean shaped structures that digest macromolecules to produce energy for the cell. • Ribosome are sites of protein synthesis and are essential to normal cell function.

31. Human Cell Composition • Lysosomes contain enzymes capable of digesting cellular fragments and in some cases the cell itself. • Lysosomes are helpful in the control of intracellular contaminates. • All structures are surrounded by membranes of lipid proteins.

32. Cellular Irradiation • When the critical macromolecular cellular components are irradiated, a dose of about 1 Mrad or 10 kGy is required to produce a measurable change in the physical characteristics of the cell.

33. Cellular Irradiation • When such a molecule is incorporated into the apparatus of a living cell, only a few rad are necessary to produce a measurable response. • Some single cell organisms require massive exposure to produce a lethal dose.

34. Cellular Irradiation • Human cells can be killed with a dose less than 100 rad (1Gy). • The nucleus is much more sensitive than the cytoplasm to radiation exposure. • Interference with any phase of protein synthesis could result in cell damage particularly DNA.

35. Cell Proliferation • Cell proliferation is the act of a single cell or group of cells reproducing and multiplying in number. • It takes many thousands of rads to disrupt macromolecules, single ionizing events to sensitive cell sites can disrupt proliferation.

36. Types of Cell Proliferation • Genetic cells (oogonium of the female and spermatogonium of the male) undergo meiosis. • Somatic cells undergo mitosis.

37. Cell Cycle • Cell biologist identify four phases of the cell cycle • Mitosis • G1 first growth • S synthesis • G2 second growth • DNA synthesis is in the S phase

38. Phases of Mitosis • Interphase has the DNA forming chromosomes. • Prophase the nucleus swells and the DNA takes a more structural form. • Metaphase the chromosomes appear and line up along the equator of the nucleus. During metaphase, mitosis can be stopped and damage analyzed.

39. Phases of Mitosis • Anaphase each chromosomes splits to form a centromere and two chromatids connected by a fiber to the poles of the nucleus. These poles are called spindles and the fiber called spindle fibers. • The number of chromosomes have been reduced by half.

40. Phases of Mitosis • The chromosomes slowly migrate toward the spindle. • Telophase is characterized by the disappearance of the chromosomes into a mass of DNA and closing off of the nucleus like a pair of dumbbells into two nuclei. The cytoplasm divides equally into two cells and interphase begins.

41. Meiosis • Genetic cell division is called meiosis. • Genetic cells begin with 46 chromosomes like somatic cells. • During the first division, the daughter, replicated the DNA with 46 chromosomes.

42. Meiosis • During the second meiosis, there is no S phase so the DNA does not replicate. Granddaughter cells have 23 chromosomes. • There is some exchange of chromosomal or crossover resulting in the genetic constitution and changes in inheritable traits.

43. Human development • During the development and maturation of a human from the two united genetic cells, a number of cell types evolve. • Collections of cells of similar structure and function form tissue. • Tissue forms organs and organs form organ systems.

44. Principle Organ Systems • Nervous System • Digestive System • Endocrine System • Respiratory System • Reproductive System • Cells of organ systems are identified by their rate of proliferation and stage of development.

45. Cell development • Underdiffentriated cell, precursor cells or stem cells are immature cells. They are more sensitive cells to radiation than mature cells. • The sensitivity of cells to radiation is determined to some degree by its state of maturity and its functional role.

46. Cell development • The tissues and organs of the body contain both stem and mature cells. • There are several types of tissue classified by their structural or functional appearance. These features influence the degree of radiosensitivity of the tissue.

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