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HUMAN RADIATION RESPONSE The effect of x-rays on humans is the result of interactions at the atomic level These atomic interactions take the form of ionization or excitation of orbital electrons and result in the deposition of energy in tissue. Deposited energy can produce a molecular change, the consequences of which can be measurable if the molecule involved is critical. When an atom is ionized, its chemical binding properties change. If the atom is a constituent of a large molecule, ionization may result in breakage of the molecule or relocation of the atom within the molecule. The abnormal molecule may in time function improperly or cease to function, which can result in serious impairment or death of the cell.
This process is reversible. Ionized atoms can become neutral again by attracting a free electron. Molecules can be mended by repair enzymes. Cell and tissues can regenerate and recover from radiation injury. If the radiation response occurs within minutes or days after the radiation exposure, it is classified as an early effect of radiation. On the other hand, if the human injury is not observed for months or years, it is called a late effect of radiation. In addition, many other radiation responses have been experimentally observed in animals. Most human responses have been observed to occur after exposure to rather large radiation doses. However, we are cautious and assume that even small doses are harmful.
The ultimate goal of radiobiologic research is to accurately describe the effects of radiation on humans so that radiation can be used more safely in diagnosis and more effectively in therapy. Most radiobiologic research seeks to develop dose-response relationships so the effects of planned doses can be predicted and the response to accidental exposure managed
COMPOSITION OF THE BODY At its most basic level, the human body is composed of atoms; radiation interacts at the atomic level. The atomic composition of the body determines the character and degree of the radiation interaction that occurs. The molecular and tissue composition defines the nature of the radiation response. More than 85% of the body consists of hydrogen and oxygen. Radiation interaction at the atomic level results in molecular change, which can produce a cell that is deficient in terms of normal growth and metabolism
Molecular Composition Five principal types of molecules are found in the body. Four of these molecules—proteins, lipids (fats), carbohydrates (sugars and starches), and nucleic acids—are macromolecules. Macromolecules are very large molecules that sometimes consist of hundreds of thousands of atoms. Proteins, lipids, and carbohydrates are the principal classes of organic molecules. An organic molecule is life-supporting and contains carbon. One of the rarest molecules—a nucleic acid concentrated in the nucleus of a cell (DNA)—is considered to be the most critical and radiosensitive target molecule.
Atomic Composition of the Body •60.0% hydrogen •25.7% oxygen •10.7% carbon •2.4% nitrogen •0.2% calcium •0.1% phosphorus •0.1% sulfur •0.8% trace elements
Molecular Composition of the Body •80% water •15% protein •2% lipids •1% carbohydrates •1% nucleic acid •1% other Water is the most abundant molecule in the body, and it is the simplest. Water, however, plays a particularly important role in delivering energy to the target molecule, thereby contributing to radiation effects. In addition to water and the macromolecules, some trace elements and inorganic salts are essential for proper metabolism.
Water The most abundant molecular constituent of the body is water. It consists of two atoms of hydrogen and one atom of oxygen (H2O) and constitutes approximately 80% of human substance. Humans are basically made of structured water. The water molecules exist both in the free state and in the bound state, that is, bound to other molecules. They provide some form and shape, assist in maintaining body temperature, and enter into some biochemical reactions. Proteins Approximately 15% of the molecular composition of the body is protein. Proteins are long-chain macromolecules that consist of a linear sequence of amino acids connected by peptide bonds. Twenty-two amino acids are used in protein synthesis, the metabolic production of proteins. The linear sequence, or arrangement, of these amino acids determines the precise function of the protein molecule. Proteins have a variety of uses in the body. They provide structure and support. Muscles are very high in protein content. Proteins also function as enzymes, hormones, and antibodies. Enzymes are molecules that are necessary in small quantities to allow a biochemical reaction to continue, even though they do not directly enter into the reaction. Hormones are molecules that exercise regulatory control over some body functions, such as growth and development. Hormones are produced and secreted by the endocrine glands—the pituitary, adrenal, thyroid, parathyroid, pancreas, and gonads.
Lipids Lipids are organic macromolecules composed solely of carbon, hydrogen, and oxygen. Lipids are present in all tissues of the body and are the structural components of cell membranes. Lipids often are concentrated just under the skin and serve as a thermal insulator from the environment. Carbohydrates Carbohydrates, similar to lipids, are composed solely of carbon, hydrogen, and oxygen, but their structure is different .This structural difference determines the contribution of the carbohydrate molecule to body biochemistry. The ratio of the number of hydrogen atoms to oxygen atoms in a carbohydrate molecule is 2:1 (as in water), and a large fraction of this molecule consists of these atoms. Consequently, carbohydrates were first considered to be watered, or hydrated, carbons, hence their name. The chief function of carbohydrates in the body is to provide fuel for cell metabolism.
Nucleic Acids Two principal nucleic acids are important to human metabolism: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Located principally in the nucleus of the cell, DNA serves as the command or control molecule for cell function. DNA contains all the hereditary information that represents a cell and, of course, if the cell is a germ cell, all the hereditary information of the whole individual. The nucleic acids are very large and extremely complex macromolecules.. DNA consists of a backbone composed of alternating segments of deoxyribose (a sugar) and phosphate. For each deoxyribose–phosphate conjugate formed, a molecule of water is removed. DNA is the radiation-sensitive target molecule
To complete the picture, the ladder is twisted about an imaginary axis such as a spring. This produces a molecule with the double-helix configuration. The sequence of base bonding is limited to adenines bonded to thymines and cytosines bonded to guanines
Human Cell The two major structures of the cell are the nucleus and the cytoplasm. The principal molecular component of the nucleus is DNA, the genetic material of the cell. The nucleus also contains some RNA, protein, and water. Most of the RNA is contained in a rounded structure, the nucleolus. The nucleolus often is attached to the nuclear membrane, a double-walled structure that at some locations is connected to the endoplasmic reticulum. This connection by its nature controls the passage of molecules, particularly RNA, from nucleus to cytoplasm The cytoplasm makes up the bulk of the cell and contains great quantities of all molecular components except DNA. A number of intracellular structures are found in the cytoplasm. The endoplasmic reticulum is a channel or a series of channels that allows the nucleus to communicate with the cytoplasm. The large bean-shaped structures are mitochondria. Macromolecules are digested in the mitochondria to produce energy for the cell. The mitochondria are therefore called the engine of the cell. The small, dot-like structures are ribosomes. Ribosomes are the site of protein synthesis and therefore are essential to normal cellular function. Ribosomes are scattered throughout the cytoplasm or the endoplasmic reticulum.
The small pea-like sacs are lysosomes. The lysosomes contain enzymes capable of digesting cellular fragments and sometimes the cell itself. Lysosomes help to control intracellular contaminants. All these structures, including the cell itself, are surrounded by membranes. These membranes consist principally of lipid-protein complexes that selectively allow small molecules and water to diffuse from one side to the other. These cellular membranes, of course, also provide structure and form for the cell and its components. When the critical macromolecular cellular components are irradiated by themselves, a dose of approximately 1 Mrad (10 kGyt) is required to produce a measurable change in any physical characteristic of the molecule.
A number of experiments have shown that the nucleus is much more sensitive than the cytoplasm to the effects of radiation. Such experiments are conducted with the use of precise microbeams of electrons that can be focused and directed to a particular cell part, or through incorporation of the radioactive isotopes tritium (3H) and carbon-14 (14C) into cellular molecules that localize exclusively to the cytoplasm or the nucleus.