Radioisotopes And Life Processes (Revised)
Renato Baserga
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Radioisotopes and Life Processes
Radioisotopes and Life Processes
The Understanding the Atom Series Nuclear energy is playing a vital role in the life of every man, woman, and child in the United States today. In the years ahead it will affect increasingly all the peoples of the earth. It is essential that all Americans gain an understanding of this vital force if they are to discharge thoughtfully their responsibilities as citizens and if they are to realize fully the myriad benefits that nuclear energy offers them. The United States Atomic Energy Commission
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THE COVER
THE COVER
The cover design portrays the inter-relationships suggested by the title of this booklet: On a trefoil symbolizing radiation are superimposed a dividing cell, a plant, an animal, and a double helix of a molecule of deoxyribonucleic acid, a material unique in and fundamental to all living things....
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THE AUTHORS
THE AUTHORS
WALTER E. KISIELESKI is an Associate Scientist in the Division of Biology and Medicine of the Argonne National Laboratory. He was formerly associate professor of chemistry at Loyola University in Chicago. His undergraduate studies were at James Millikin University in Decatur, Illinois, and his graduate studies were at the University of Chicago. He received an Honorary Doctor of Science degree from James Millikin University in 1962. In 1958 he was a delegate to the Second Atoms for Peace Conferen
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INTRODUCTION
INTRODUCTION
Here and elsewhere we shall not obtain the best insight into things until we actually see them growing from the beginning. Aristotle The nature of life has excited the interest of human beings from the earliest times. Although it is still not known what life is, the characteristics that set living things apart from lifeless matter are well known. One feature common to all living things, from one-celled creatures to complex animals like man, is that they are all composed of microscopic units know
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Unit of Life
Unit of Life
The cell theory, based on the concept that higher organisms consist of smaller units called cells, was formulated in 1838 by two German biologists, Mathias-Jacob Schleiden, a botanist, and Theodor Schwann, an anatomist. The theory had far-reaching effect upon the study of biological phenomena. It suggested that living things had a common basis of organization. Appreciation of its full significance, however, had to await more precise knowledge of the structure and activities of cells. Some organi
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Cell Structure
Cell Structure
Figure 2 Generalized diagram of a cell, showing the organelles, or “little organs”, of its internal structure. The organelles that are labeled are important for this booklet. The basic structure of a cell is shown in Figure 2 . Each cell consists of a dense inner structure called the nucleus, which is surrounded by a less dense mass of cytoplasm. The nucleus is separated from the cytoplasm by a double envelope, called the nuclear membrane, which is peppered with perforations. The cytoplasm conta
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The Two Nucleic Acids
The Two Nucleic Acids
It is not very fruitful to discuss whether proteins or nucleic acids are more important. That question is something like the one about the chicken and the egg. We cannot think of one without thinking of the other. Although our insight into the mutual dependence of these two materials has greatly increased in recent years and although we know the relation between them is a fundamental factor in such events as reproduction, mutation, and differentiation (or specialization) of cells, our understand
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Mitosis
Mitosis
One of the most remarkable characteristics of cells is their ability to grow and divide. New cells come from preexisting cells. When a cell reaches a certain stage in its life, it divides into two parts. These parts, after another period of growth, can in turn divide. In this way plants and animals grow to their normal size and injured tissues are repaired. Cell division occurs when some of the contents of the cell have been doubled by replication, or copying (to be discussed later). The divisio
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Atomic Structure
Atomic Structure
Practically everyone nowadays is to some extent familiar with the atomic structure of matter. Atomic energy, nuclear reactors, and radioisotopes are terms in everyday usage. However, to appreciate how radioisotopes can be applied to the study of life processes, we must have at least a working knowledge of their properties, their preparation, and their limitations. It is therefore appropriate to examine them in detail so that the succeeding chapters will be more easily understood. According to pr
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Isotopes
Isotopes
Atoms of the same element, that is, atoms with the same number of protons and electrons, may vary slightly in mass because of having different numbers of neutrons. Since the chemical behavior of an element depends upon its electrons’ electrical charges, extra neutrons (which do not have an electrical charge) may affect the mass of an atom without disturbing its chemical properties. Atoms having the same atomic number but different atomic weights are called isotopes. For example, as shown in Figu
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Radioactive Isotopes
Radioactive Isotopes
Radioactive isotopes occur as minor constituents in many natural materials, from which they can be concentrated by fractionation procedures. In a very limited number of cases, more significant amounts of a radioactive isotope, for example, radium or radioactive lead, can be found in nature. Most radioactive isotopes in use today, however, are prepared artificially by nuclear reactions. When a high-energy particle, such as a proton, a deuteron, an alpha particle, or a neutron, collides with an at
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Radioactive Isotopes’ Value in Biological Studies
Radioactive Isotopes’ Value in Biological Studies
To biologists, then, the essential feature in the use of radioactive isotopes is the possibility of preparing “labeled” samples of any organic molecule involved in biological processes. With labeled samples it is possible to distinguish the behavior and keep track of the course of molecules involved in a particular biological function. In this capacity the isotope may be likened to a dynamic and revolutionary type of “atomic microscope”, which can actually be incorporated into a living process o
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DNA in Somatic and Germinal Cells
DNA in Somatic and Germinal Cells
One of the fundamental laws of modern biology—which states that the DNA content of somatic cells is constant for any given species—was first set forth in a research report of 1948. This finding means that in any given species, such as a mouse or a man, all cells except the germinal cells contain the same amount of DNA. Germinal cells, that is, the sperm cells of the male semen and the female egg, contain exactly half the amount of DNA of the somatic cells. This must be the case, since DNA is the
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Replication of DNA
Replication of DNA
Figure 11 is a diagram showing the essential structure of the large DNA molecule. According to the Watson-Crick model, [7] the molecule consists of two strands of smaller molecules twisted around each other to form a double helix. Each strand consists of a sequence of the smaller molecules linked linearly to each other. These smaller molecules are called nucleotides, and each consists of three still smaller molecules, a sugar (deoxyribose), phosphoric acid, and a nitrogen base. Each nucleotide a
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Labeling DNA with a Radioactive Isotope
Labeling DNA with a Radioactive Isotope
Of the four bases in DNA, three are also found in the other nucleic acid, RNA; but the fourth, thymine, is found only in DNA. Therefore, if thymine could be labeled and introduced into a number of cells, including a cell in which DNA is being formed, we would specifically label the newly synthesized DNA, since neither the old DNA nor the RNA would make use of the thymine. We could in this way mark cells preparing to divide. (Actually, thymine itself is not taken up in mammalian cells, but its nu
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Detecting DNA with Autoradiography
Detecting DNA with Autoradiography
Autoradiography is based on the same principle as photography. Just as photons of light impinging on a photographic emulsion produce an image, so do beta particles (or alpha particles) emitted by decomposing radioactive atoms. A photographic emulsion is a suspension of crystals of a silver halide (usually silver bromide) embedded in gelatin. When crystals of silver bromide are struck by beta particles, the silver atoms are ionized and form a latent image, so called because it is invisible to our
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Three Kinds of RNA
Three Kinds of RNA
In the first place, there are at least three different kinds of RNA. The largest quantity is a special kind called ribosomal RNA, or r-RNA. It is found in close conjunction with proteins and makes up the structural frame upon which the protein-synthesizing machinery is built. The r-RNA and the proteins to which it is firmly bound form the ribosomes, the RNA-rich microsomes that are attached to the endoplasmic reticulum. Proteins are synthesized on ribosomes. We shall see later what determines th
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Labeling RNA with a Radioactive Isotope
Labeling RNA with a Radioactive Isotope
RNA synthesis is investigated with radioactive tracers in the same way as DNA synthesis. If we can mark, with a radioactive atom, a small molecule that is incorporated into newly formed RNA, we can then trace the course of the labeled RNA molecule with a radiation-detection device. DNA had one advantage in this regard—the fact that one compound, thymidine, was a precursor of DNA, a specific material that could be incorporated only into DNA. We do not know similar specific precursors of RNA. But
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Detecting RNA with Autoradiography
Detecting RNA with Autoradiography
As in DNA synthesis, we can use autoradiography to follow the incorporation of precursors into RNA. By proper treatment of the tissues, we can make sure that all the radioactivity visible by autoradiography is due to labeled RNA, even though some of the precursor also enters DNA molecules. Even so, the kind of information obtained from autoradiographs of tissues exposed to RNA precursors is different from that obtained with DNA precursors. The advantage of high-resolution autoradiography in DNA
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Other Methods of Detecting RNA
Other Methods of Detecting RNA
If we look at cells soon after they have been exposed to an RNA precursor, we find that the radioactivity detectable by autoradiography is only in the nuclei of the cells. No radioactivity can be detected in the cytoplasm, although we know that the cytoplasm of living cells contains large amounts of r-RNA and s-RNA. One or two hours later, however, radioactive RNA appears in the cytoplasm as well as in the nucleus. What autoradiography is telling us is that RNA is made in the nucleus and then is
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Amino Acids and Protein Structure
Amino Acids and Protein Structure
Amino acids are the fundamental structural units of proteins. There are 20 amino acids found frequently in mammalian proteins, and these molecules may be linked to one another to form a chain called a polypeptide chain. The structure of a protein then depends on: (1) the quantity of each amino acid present; (2) the sequence of amino acids in the polypeptide chain; (3) the length of the polypeptide chain, that is, the molecular weight; and (4) the folding and the side (nonlinear) arrangement of t
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Labeling an Amino Acid with a Radioactive Isotope
Labeling an Amino Acid with a Radioactive Isotope
Suppose we have the amino acid leucine labeled with ¹⁴C and we inject a solution containing it into an experimental animal. Since leucine is incorporated into proteins, if we isolate the proteins and determine both the amount of proteins and the amount of radioactivity, we can measure fairly accurately the rate of protein synthesis. Autoradiography, by the way, is of little help in studying most protein synthesis because all cells are always synthesizing proteins and so are all labeled after a s
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Interphase
Interphase
Until a few years ago, we knew very little about interphase. In fact, in one classic book on histology, [8] while a description of mitosis required almost 12 pages, interphase was dismissed in less than six lines! The reason for this lack of interest was, of course, the fact that no adequate methods were available for studying metabolic activities of cells in interphase. The methods of high-resolution autoradiography and radiochemical analysis of synchronized cell populations have become availab
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The Cell Cycle
The Cell Cycle
Figure 25 is a diagram of the cell cycle. Try to imagine the cell cycle as a race track and individual cells as cars that race around it. You are sitting at the finish wire, which is mitosis (we chose mitosis because it is easy to recognize when the cell is observed with the aid of a microscope). At a certain time during the race, all the cars in a portion of the track, say a 200-yard sector of the backstretch, are sprayed with a blue dye as they race by. These cars are now marked, just as cells
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DNA Synthesis and the Cell Cycle
DNA Synthesis and the Cell Cycle
Because it has several important implications in biology and medicine, it is important to remember that DNA synthesis occurs only during the short, well-defined S period of the cell cycle. Other synthetic processes go on throughout the cycle. We mentioned, for instance, that all cells can be labeled by a brief exposure to a radioactive amino acid, a precursor of proteins; this means that protein synthesis occurs throughout the entire cell cycle, including mitosis. When we use a radioactive RNA p
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Translation of the Genetic Message
Translation of the Genetic Message
The DNA of a particular active gene manufactures a molecule of m-RNA by the same kind of replication that it uses for making more DNA. In m-RNA the sequence of bases is the same as in the parent DNA segment; for this reason, m-RNA is also called DNA-like RNA. As shown in Figure 12 , a cytosine molecule in m-RNA corresponds to a cytosine molecule in DNA, a guanine to a guanine, and so on, except that the m-RNA has uracil in all the places where thymine occurs in DNA. The order of the nucleotides
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ISOTOPES IN RESEARCH: PROBING THE CANCER PROBLEM
ISOTOPES IN RESEARCH: PROBING THE CANCER PROBLEM
... a riddle wrapped in a mystery inside an enigma. Winston Churchill The various procedures in which radioactive isotopes play a major role have been applied to many studies and investigations in the fields of biology and medicine. In fact, most of the concepts of modern biology that we have been discussing in this booklet owe their discovery to the judicious use of radioisotopes. To illustrate how radioisotopes can be used to solve a practical problem, we have chosen a typical example, the inv
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CONCLUSIONS
CONCLUSIONS
Thus, the task is, not so much to see what no one has seen yet; but to think what nobody has thought yet, about what everybody sees. Arthur Schopenhauer The use of radioactive isotopes in the study of life processes is of importance in understanding them. With the use of autoradiographic and radiochemical techniques, it is possible to obtain valuable information regarding the life of cells and the intimate mechanisms by which life processes determine the fate of the entire organism. Our knowledg
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Books
Books
The Cell , Carl P. Swanson, Prentice-Hall, Inc., Englewood Cliffs, New Jersey, 1964, 114 pp., $1.75. Inside the Living Cell , J. A. V. Butler, Basic Books, Inc., New York, 1959, 174 pp., $3.95. Life and Energy , Isaac Asimov, Doubleday & Company, Inc., Garden City, New York, 1962, 380 pp., $4.95. Applied Nuclear Physics , Ernest C. Pollard and William L. Davidson, John Wiley & Sons, Inc., New York, 1956, 352 pp., $6.00. Adventures in Radioisotope Research , the collected works, w
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Articles
Articles
Autobiographies of Cells, R. Baserga and W. Kisieleski, Scientific American , 209: 103 (August 1963). Electrons, Enzymes, and Energy, Michael G. Del Duca and John M. Fuscoe, International Science and Technology , 39: 56 (March 1965). Scientific American , 205 (September 1961). This is a special issue on the living cell. The two articles cited below are of particular interest:...
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Reports
Reports
Liquid Scintillation Counting: Proceedings of a Conference Held at Northwestern University, August 20-22, 1957 , C. G. Bell, Jr. and F. N. Hayes (Eds.), Pergamon Press, Inc., New York, 1957, 292 pp., $10.00. Atomic Energy Research: Life and Physical Sciences; Reactor Development; and Waste Management , A Special Report of the U. S. Atomic Energy Commission (December 1961), Superintendent of Documents, U. S. Government Printing Office, Washington, D. C. 20402, 333 pp., $2.25....
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Booklets
Booklets
Radioisotopes in the Service of Man , Fernand Lot, National Agency for International Publications, 317 East 34th Street, New York 10016, 1958, 82 pp., $1.00. Science and Cancer , M. B. Shimkin, Public Health Service Publication No. 1162, Superintendent of Documents, U. S. Government Printing Office, Washington, D. C. 20402, 1964, 137 pp., $0.60....
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Motion Pictures
Motion Pictures
The Cell: Structural Unit of Life , 10 minutes, sound, color or black and white, 1949, Coronet Films, Inc., 65 E. South Water Street, Chicago, Illinois 60601. Continuity of Life: Characteristics of Plants and Animals , 11 minutes, sound, color or black and white, 1954, Audio-Visual Center, Indiana University, Bloomington, Indiana 47405. DNA: Molecule of Heredity , 16 minutes, sound, color (No. 1825), black and white (No. 1826). 1960, Encyclopaedia Britannica Films, Inc., Wilmette, Illinois 60091
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PHOTO CREDITS
PHOTO CREDITS
This booklet is one of the “Understanding the Atom” Series. Comments are invited on this booklet and others in the series; please send them to the Division of Technical Information, U. S. Atomic Energy Commission, Washington, D. C. 20545. Published as part of the AEC’s educational assistance program, the series includes these titles: A single copy of any one booklet, or of no more than three different booklets, may be obtained free by writing to: USAEC, P. O. BOX 62, OAK RIDGE, TENNESSEE 37830 C
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