Contemporary Radiobiology

By Kenshi Komatsu

Contemporary Radiobiology

By Kenshi Komatsu

This book first published 2019

Cambridge Scholars Publishing

Lady Stephenson Library, Newcastle upon Tyne, NE6 2PA, UK

British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library

Copyright © 2019 by Kenshi Komatsu

All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner.

ISBN (10): 1-5275-3882-6 ISBN (13): 978-1-5275-3882-5 CONTENTS

Preface ...... xiv

Part I: Physical Properties of

Chapter One ...... 2 The Nature of Radiation 1.1 The discovery of radiation 1.1.1 Radiation and radioactivity 1.1.2 Different types of radiation and their penetration abilities 1.2 Mechanisms of ionization and radiation units 1.2.1 How radiation causes ionization 1.2.2 Radioactivity and radiation units 1.3 Radiation 1.3.1 Radiation dosimeters which use ionization 1.3.2 Radiation dosimeters using semiconductors 1.3.3 Radiation dosimeters which use scintillation 1.3.4 Radiation dosimeters that utilize emission from glass 1.3.5 and counting efficiency Commentary 1: Another Poincaré conjecture

Chapter Two ...... 21 Utilizing Nuclear reactions 2.1 Natural decay of 2.1.1Types of nuclear decay and the radioactive nucleus 2.1.2 Natural decay of radionuclides and half-lives 2.2 Mechanisms of generation and waste disposal 2.2.1 Artificial 2.2.2 How a nuclear power plant generates electricity 2.2.3 The nuclear fuel cycle 2.2.4 Waste disposal problems 2.3 Military uses of nuclear reactions 2.3.1 Nuclear fission used in A-bombs 2.3.2 used in H-bombs 2.4 Industrial and academic uses of radiation 2.4.1 Industrial applications vi Contents

2.4.2 Agricultural uses 2.4.3 Commentary 2: Decimal notation for half-lives Questions & Answers

Part II: Radiation and Biology

Chapter Three ...... 46 Effect of Radiation on Cells 3.1 Cleavage of DNA strands by radiation 3.1.1 Time course of radiation’s biological actions 3.1.2 DNA damage is caused by direct and indirect action 3.1.3 The chemical structure at the ends of DNA strand breaks 3.2 Mathematical models and the evaluation of biological effects 3.2.1 Reproductive death measured with the colony assays 3.2.2 SLD recovery is an indicator of the effects of chronic 3.2.3 Mathematical descriptions of cell survival curves 3.3 Factors that modify biological effects 3.3.1 Radioprotectors and mitigators can reduce radiation effects 3.3.2 Oxygen enhances radiation effects 3.3.3 Differences in biological effects due to (LET) Commentary 3: Radicals and the ozone hole

Chapter Four ...... 67 DNA Repair and Protection from Radiation 4.1 Repair of DNA double-strand breaks 4.1.1 Studies of repair pathways using radiation sensitive cells 4.1.2 Two types of DNA repair are involved in the rejoining of DNA double-strand breaks 4.2 Initial cellular responses to DNA double-strand breaks 4.2.1 Checkpoints to a pause in cell proliferation 4.2.2 Chromatin remodeling relaxes DNA structures 4.2.3 promotes rather than DNA repair 4.3 Side effects of DNA repair 4.3.1 Variation of radiation sensitivity in the cell cycle and SLD recovery 4.3.2 Radiation mutagenesis Commentary 4: Gene nomenclature and protein designation Commentary 5: Why do elephants not develop more often Contemporary Radiobiology vii

Chapter Five ...... 87 Radiation Injuries to Tissues and Organs 5.1 Deterministic effects and effects 5.1.1 Radiation injuries are classified into deterministic effects and stochastic effects 5.1.2 Radiation sensitivity varies among tissues 5.1.3 Onset of radiation injuries 5.2 Radiation injuries in various organs 5.2.1 Skin injuries 5.2.2 Injuries to the testes and ovaries 5.2.3 Eye injuries 5.2.4 Others organs: , kidney, , oral mucosa 5.3 Injuries to three critical organs which can lead to individual deaths after radiation exposures 5.3.1 Relationship between exposure dose and survival time 5.3.2 marrow death 5.3.3 Intestinal death 5.3.4 death 5.3.5 Clinical treatments for radiation accidents at doses approaching LD50/60 Commentary 6: Stem cells, ES cells and iPS cells Commentary 7: Leukemia and the

Chapter Six ...... 109 Radiation Carcinogenesis 6.1 The nature of spontaneous carcinogenesis and radiation carcinogenesis 6.1.1 Activation of oncogenes and the inactivation of tumor suppressor genes 6.1.2 Mechanisms leading to spontaneous carcinogenesis 6.1.3 Mechanisms involved in radiation carcinogenesis 6.2 of radiation carcinogenesis in humans 6.2.1 Useful epidemiological data 6.2.2 Development of leukemia 6.2.3 Development of solid 6.3 Factors affecting radiation carcinogenesis 6.3.1 Effect of age at exposure 6.3.2 Effect of chronic exposures and the type of radiation 6.3.3 Other factors affecting radiation carcinogenesis 6.4 Radiation carcinogenesis risk and the LNT hypothesis 6.4.1 What is the LNT hypothesis viii Contents

6.4.2 Using the LNT model avoids unnecessary risks from exposures Commentary 8: Terms used to describe carcinogenesis and Commentary 9: Local distribution of deaths from spontaneous carcinogenesis in Japan

Chapter Seven ...... 129 Radiation and Birth Defects 7.1 The radiation sensitive fetal stage 7.1.1 Embryo death during the pre-implantation period 7.1.2 Congenital malformations during organogenesis 7.1.3 Microcephaly in the fetus 7.2 How hereditary effects occur 7.2.1 Chromosomal abnormalities due to radiation exposures 7.2.2 Mendelian inheritance in a single gene 7.2.3 Human hereditary 7.3 Unexpectedly low risk of radiation-induced hereditary diseases 7.3.1 Methods used to estimate hereditary risk 7.3.2 The doubling dose for genetic mutations in mice 7.3.3 Evaluation of radiation risks for hereditary diseases 7.3.4 Hereditary effects have not been observed in A-bomb survivors 7.3.5 Radiation carcinogenesis in the fetus and trans-generational carcinogenesis Questions & Answers

Part III: Radiation and

Chapter Eight ...... 154 Tumor Radiotherapy 8.1 Tumor radiobiology 8.1.1 Radiation is effective for treating tumors 8.1.2 Hypoxic cells and radiotherapy 8.1.3 Radiation sensitivity in tumors 8.1.4 Tolerable doses for normal organs 8.2 Modification of radiation sensitivity in tumors and normal tissues 8.2.1 Sequential reoxygenation of hypoxic cells 8.2.2 Combining antitumor drugs with radiotherapy 8.2.3 Reducing damage to normal tissues Contemporary Radiobiology ix

8.3 Alternative radiation modalities for tumor treatment 8.3.1 Three-dimensional conformal radiotherapy 8.3.2 Intensity modulated radiotherapy 8.3.3 Stereotactic radiotherapy 8.3.4 beam therapy 8.3.5 Heavy particle beam therapy 8.3.6 with small shielded radiation sources 8.3.7 capture therapy

Chapter Nine ...... 177 Diagnostic Uses of Radiation 9.1 Types of X-ray Diagnosis 9.1.1 Principles of X-ray photography 9.1.2 X-ray generators 9.1.3 Detecting X-rays 9.1.4 9.1.5 X-ray CT 9.1.6 Interventional 9.2 Diagnosis using radionuclides 9.2.1 Single photon emission computed tomography (SPECT) 9.2.2 emission tomography (PET) 9.3 Exposure doses received from diagnostic radiation Commentary 10: The Beatles and X-ray CT Questions & Answers

Part IV: Life and Radiation

Chapter Ten ...... 202 DNA Base Repair and Life 10.1 Protecting DNA from solar light and smoking 10.1.1 Types of DNA base damage induced by solar ultraviolet light 10.1.2 DNA base damage due to smoking 10.1.3 Nucleotide excision repair 10.1.4 Translesion DNA synthesis 10.1.5 Skin cancer and Xeroderma Pigmentosum 10.2 Protecting DNA from oxygen toxicity 10.2.1 DNA base damage produced by oxidation 10.2.2 Base excision repair 10.2.3 Base excision repair and carcinogenesis x Contents

10.3 Protecting DNA from alcohol-induced damage 10.3.1 DNA interstrand cross-links are caused by alcohol metabolism 10.3.2 DNA interstrand cross-links and Fanconi Anemia 10.4 Correcting DNA replication errors 10.4.1 Incorrect DNA base incorporation 10.4.2 Mismatch repair 10.4.3 Familial colorectal cancer and mismatch repair 10.5 Clustered DNA damage caused by radiation 10.5.1 DNA base damage caused by radiation 10.5.2 Radiation-specific clustered DNA damage Commentary 11: A national fungus in Japan

Chapter Eleven ...... 221 Life on Earth and the Repair of DNA Double-strand Breaks 11.1 Origin of DNA double-strand break repair 11.1.1 Life on the earth and solar ultraviolet light 11.1.2 Life on earth and radiation 11.1.3 Origin of the repair proteins involved in DNA double-strand break repair 11.1.4 Generation of DNA double-strand breaks by agents other than radiation 11.2 DNA repair pathways involved in evolution 11.2.1 Translesion DNA synthesis can lead to mutations 11.2.2 Homologous recombination and genetic diversity 11.3 Repair proteins which function in the maintenance of health 11.3.1 Immune diversity and non-homologous end-joining 11.3.2 Carcinogenic barriers and signals 11.3.3 Telomere maintenance and ATM 11.3.4 Control of antioxidants and diabetes by ATM Commentary 12: Darwin, Mendel, and Miescher were pioneers in the same era Questions & Answers

Part V: Nuclear Disasters and

Chapter Twelve ...... 242 Accident at the Fukushima Daiichi Nuclear Power Plant 12.1 Outline of the accident 12.1.1 Structure of emergency cooling systems and container venting Contemporary Radiobiology xi

12.1.2 The earthquake and the station blackout 12.1.3 Evacuation of the public within 3 km 12.1.4 Expanding the evacuation area to 10 km 12.1.5 Expanding the evacuation area to 20 km 12.1.6 Public indoor sheltering within 20-30 km 12.2 Lessons from the accident 12.2.1 Location of the NPP and measures to protect against a tsunami 12.2.2 Measures to protect against a power loss 12.2.3 Venting design 12.2.4 Resident evacuation 12.2.5 Remarks 12.3 Radioactive contamination and food regulation 12.3.1 Radioactive material which was released 12.3.2 Environmental behavior of radioactive cesium and radiation doses 12.3.3 Food and regulations 12.3.4 Drinking water 12.3.5 New regulations 12.3.6 Calculation of regulation levels of Cesium-137 in diets 12.4 Exposure dose and health surveys 12.4.1 Exposure doses delivered to residents 12.4.2 Health survey of residents 12.4.3 Exposure doses and health surveys of workers Commentary 13: Maximum record of the internal radiation exposure in Japan

Chapter Thirteen ...... 268 Nuclear Disasters and Related Accidents around the World 13.1 A-bombs and nuclear tests 13.1.1 A-bombs at Hiroshima and Nagasaki 13.1.2 Nuclear tests at the Bikini Atoll 13.1.3 Nuclear tests in China 13.1.4 Nuclear tests in Semipalatinsk 13.2 Nuclear power plant accidents around the world other than Fukushima 13.2.1 Accident at the NPP 13.2.2 Accident at Three Mile Island 13.3 Exposures at nuclear fuel processing facilities 13.3.1 reprocessing plant 13.3.2 The Hanford nuclear site xii Contents

13.3.3 The Majak nuclear plant 13.3.4 The Tokai-Mura

Chapter Fourteen ...... 287 Radiation in Our Environment 14.1 Public exposures from natural radiation 14.1.1 Natural radiation sources and artificial radiation sources 14.1.2 Radiation sources in the earth 14.1.3 Radiation sources in the air 14.1.4 Radiation sources in food 14.1.5 Cosmic radiation 14.1.6 Exposures from consumer goods 14.2 Occupational exposures from natural and artificial radiation sources 14.2.1 Exposures from natural radiation sources in mines 14.2.2 Exposure to cosmic radiation during international flights 14.2.3 Exposures from artificial radiation sources 14.3 Survey of health effects in high radiation areas 14.3.1 High radiation areas around the world 14.3.2 Health surveys of populations Commentary 14: -210 and a spy

Chapter Fifteen ...... 305 Radiation Protection and Risk Management 15.1 Principles of radiation protection 15.1.1 Features of external exposures and protection 15.1.2 Characteristics of internal exposures and protection 15.2 Agents that decrease radioactivity levels in the body 15.2.1 iodide reduces the uptake of radioactive iodine 15.2.2 Prussian blue is effective to help excrete radioactive cesium 15.3 Living in radiation contaminated areas 15.3.1 Decontamination around residences 15.3.2 Countermeasures used to minimize radiation exposures in a residence 15.4 Radiation protection and legal regulations 15.4.1 Basic concepts of the ICRP and its recommendations 15.4.2 History of occupational dose limits 15.4.3 History of public dose limits 15.4.4 Legislation to prevent radiation hazards from endangering the public in Japan Contemporary Radiobiology xiii

15.5 Nuclear disarmament trends around the world Commentary 15: The tragedy of the dial painters Questions & Answers


Appendix 1 ...... 334 Signs of DNA Double-strand Breaks remain in Cells

Appendix 2 ...... 337 Evidence that DNA Double-strand Breaks cause Human Carcinogenesis

Appendix 3 ...... 340 Bioaccumulation of Cesium-137

Index ...... 344 PREFACE

Japan has an unfortunate history of radiation exposures, such as the A- bomb disaster, fishermen's exposures at the Marshal atolls, the JCO criticality accident at Tokai village, and the unprecedented nuclear power plant accident at the Fukushima Daiichi Nuclear Power Plant, where three nuclear reactors consecutively lost their cooling capacity after the earthquake and tsunami on March 11, 2011. In Fukushima, one hundred forty thousand residents were forced to leave their homes, suffered from anxiety over possible late radiation effects, and also suffered from the loss of their economic communities and their social communities. There are presently plans for more than 50 reactors to be operated in Japan. Worldwide, there are more than 10,000 nuclear weapons, mainly in the and Russia, and these present potential sources of harm to mankind. On the other hand, medical diagnoses using radiation are made in 3.65 billion cases each year around the world, and these medical exposures have become a major source of radiation exposures. The earth was created through the accumulation of material from nuclear reactions that occurred in a corner of the galaxy. Although this nuclear event was about 4.8 billion years ago, radioactive substances from that event are still sources of ground radiation and gas in the earth. In addition, recent observations of from deep in the earth confirmed that those radioactive substances supply the enormous heat (decay heat) in the earth, in addition to the gravitational energy present at the birth of the earth. This heat moves the continental plates which then causes earthquakes and tsunami, and such events eventually led to disasters such as the accident at the Fukushima Daiichi Nuclear Power Plant. Even today, people are surrounded by natural radiation sources and artificial radiation sources, and it seems like a good idea that they should be able to have a minimum of knowledge about the nature of radiation, its deleterious effects on health, and how we can protect ourselves from radiation. The reason I decided to write this book was the occurrence of the accident at the Fukushima Daiichi Nuclear Power Plant. In lectures given after the accident, I realized that there should be some information or sources that covered the subject of radiation biology, and which could be shared by lecturers, doctors, researchers, students, administrators, and citizens who were concerned about the use and presence of radiation. For Contemporary Radiobiology xv that reason, this book was intended to present the current state of knowledge about radiation for non-experts, and also to describe the latest scientific findings in the fields of radiation and medicine. Moreover, because of the initial purpose of this publication, this book also focuses on past nuclear disasters and radiation currently present in our environment. As a result, the contents of the book cover a vast range of subjects going from Chapter 1 (the physics of radiation) to the end of Chapter 15 (nuclear disarmament). These chapters are grouped into five parts, and readers can choose to read the individual sections which they find are of interest to them. Part I describes the “Physical Properties of Radiation” for people whose interests focus on the measurement of radiation, nuclear power plants etc. Similarly, Part II “Radiation and Biology”, Part III “Radiation and Medicine”, and Part IV “Life and Radiation” should be of interest to those who want to learn about the deleterious effects of radiation, the mechanisms involved in the medical use of radiation, and the life sciences and radiation, respectively. If one is interested in past nuclear disasters and radiation protection, Part V “Nuclear Disasters and Radiation Protection” should be of interest. In order to help understand the contents of the book, there are “Commentary” sections related to the material in some of the chapters. In addition, Appendices and “Questions and Answers”are also provided in the book. This book was published with the help of Lonnie Kapp, who edited the English version of the Japanese book, “Contemporary Radiobiology” (Kyoto University Academic Press, 2017). I also thank Tetsuya Ono (in the Environmental Science and Technology Research Institute), Akira Endo (Hiroshima University), Hiroshi Fukuda and Akihiro Kato (Tohoku Medical and Pharmaceutical University), Shizuko Kakinuma (National Institute of Radiological Sciences), Hiroshi Tauchi (Ibaraki University), Sachiko Hamajima (Tokyo Nuclear Services Co., Ltd.), Masayoshi Yamamoto (Kanazawa University), Masao Yoshimura and Junya Kobayashi (Kyoto University), Kazuo Ogai (the city office in Minami- Soma City), and also would like to thank Ms. Nagano at Kyoto University Academic Press, who helped prepare the Japanese version.

March 11, 2019 Radiation Biology Center, Kyoto University





There are different types of radiation: electromagnetic waves such as X-rays and γ-rays, and particle beams such as α-rays and β-rays. All of these different types of radiation can collide or interact with and cause ionization and light emission. Therefore, the quantity of radiation can be easily measured with detection instruments capable of measuring ionization and light emission events. Here, we describe the basic properties of radiation, such as ionization, and describe the radiation units used in observing biological effects, and the associated measurement methods.

1.1 The discovery of radiation 1.1.1 Radiation and radioactivity

Radiation is present in our daily lives as part of our natural environment, and is also used for medical and industrial purposes. However, it was only relatively recently that society began to understand and use radiation and, as happend with other scientific findings, this discovery was an accidental event. Wilhelm C. , a professor of physics at the University of Wuerzburg (Fig. 1.1a) studied beams generated by a Crookes tube with a positive pole (anode) and a negative pole (cathode) (see Chapter 9.1.2). When a high voltage was applied across these poles, Roentgen noticed that fluorescent material located in his lab at a distance from the Crookes tube emitted light or fluorescence, even after the material was covered with black paper. This was due to a new type of radiation which was transmitted through the glass of the Crookes tube. Roentgen first reported this in the Journal of the Wuerzburg Physical Medical Society. The article was "Über eine neue art von strahlen" or “Describing a new type of radiation” and was dated December 28, 1895. This new radiation was called "X-rays" using the symbol X which represented unknown quantities in mathematics. The paper was accompanied by an X-ray photograph of his wife's hand, suggesting that The Nature of Radiation 3 he was thinking about possible medical applications almost immediately after his discovery. Indeed, the usefulness of X-rays in medicine was discussed at a meeting of the Berlin Internal Medicine Society early in the New Year of 1896, and on January 23, Roentgen himself gave a lecture at the Wuerzburg Physical Medical Society. In his lecture, he discussed the ability of X-rays to travel through the human body, and also circulated X- ray photographs of a participant’s hand (Fig. 1.1b). This was an exciting discovery, and the discovery of this new type of radiation earned Roentgen the honor of receiving the First .

(a) レントゲン教授 (b) X 線発見当時の写真 (a) Prof. Roentgen (b) X-ray photograph

Figure 1.1 Photo of Prof. Roentgen and an X-ray photograph. (a) A Photo of Prof. Wilhelm Conrad Roentgen at the University of Wurzburg, Germany (Courtesy of U.S. National Library of Medicine). (b) an X-ray photograph of a participant's hand circulated in Roentgen’s lecture on January 23, 1896. (Courtesy of the University of Wurzburg).

The following year, in 1896, Antoine H. (France) reported that radiation from natural ore has properties similar to X-rays. This new type of radiation was called Becquerel rays and was not initially identified as being X-rays (Commentary 1). As a result of this discovery, Becquerel’s name was chosen to represent a unit of radioactivity (see Chapter 1.1.2). Eventually it was discovered that Becquerel’s rays were not a single type of radiation. Based on differing abilities to penetrate different substances, Earnest deduced that there were more than two types of radiation present in Becquerel rays, and in 1898 he named them α-rays and β-rays, respectively (Fig. 1.2). Two years later, another researcher found a third type of radiation with a high penetration ability and named this third form of radiation γ-rays following advice from 4 Chapter One

Rutherford. These α-rays, β-rays and γ-rays are generated through the nuclear decay of radioactive elements (see Chapter 2), and this is a different mechanism from that which generates X-rays.

Proton Neutron α-rays

Helium nuclues

β-rays Electron

γ-rays, X-rays Electromagnetic waves

Paper Aluminium plate Lead plate

Figure 1.2 Several types of radiation and their penetrating abilities. Although particle beams, including α-rays and β-rays, can be completely shielded by paper or a thin aluminum foil, a thick lead block is necessary to provide a shield against γ-rays or electromagnetic waves.

Commentary 1. Another Poincaré conjecture

Henri Poincaré is a French mathematician and physicist who lived in the latter part of the 19th century. The Poincaré conjecture is famous for being the Millennium Prize Problem which was a major mathematical problem in topology. There was a prize of $1,000,000 for someone who could solve the problem. It was solved by the Russian mathematician, Grigori Perelman, in 2002 after 100 years, but he received a great deal of attention when he refused the prize money. However, from Poincaré’s standpoint of emphasizing intuition, he made other predictions besides his famous conjecture. Another Poincaré prediction was made immediately after a report by Roentgen. At the Institute of France, Poincaré speculated on the possibility that substances which were able to emit fluorescent light also had the ability to emit X-rays along with having fluorescence properties. Bequerel was inspired by this lecture and tried to detect X-rays in fluorescent uranium ore in . However, he discovered that radiation was emitted in the absence of sunlight. Since this was only two months after the discovery of X-rays, people speculated that there was a fierce research competition between these two people concerning the discovery of radiation. The fact is that the discovery of Becquerel rays was triggered by Poincaré's intuition after a report by Roentgen. The Nature of Radiation 5

Mrs. Marie (France) was interested in the new radiation discovered by Becquerel, and tried to separate and refine pitchblende ore, which emits radiation similar to that emitted from uranium ore, and reported in 1898 that there were two types of radioactive elements, Polonium and . Polonium was named after ’s native country Poland, and Radium is the Latin word for radiation. Mrs. Curie also succeeded in developing a method to quantitatively measure the amount of ionization produced by radiation by using a quartz plate piezoelectric meter which was prepared by her husband Pierre. From her studies, it was found that the amount of radiation present was not dependent on the ambient temperature and light, but only on the amount of the radioactive substance present, such as uranium or radium. This was also the first time the word “radioactivity” was used to denote ionization. To discuss radiation, it is necessary to define differences in the meanings of the words radioactivity, radioactive substances (elements), and radiation (such as X-rays). These relationships can be illustrated by comparing these terms with a bonfire (Fig. 1.3).

Heating power Radioactivity Thermal rays Radiation

Radiactive Wood materials

Figure 1.3 Radiation and radioactivity. Radiation and radioactivity are illustrated by comparisons to a bonfire. The bonfire’s power and its () thermal rays correspond to radioactivity and radiation, respectively.

Radiation consists of electromagnetic waves or particle beams that are generated by either X-ray tubes or radioactive material. It is sometimes referred to as to distinguish it from electromagnetic waves such as ultraviolet light which does not cause ionization. One can think of radiation as being the equivalent of (infrared) thermal rays emitted from a bonfire. Atoms with a non-neutral charge are called ionized (additional details are shown on Chapter 1.1.2). 6 Chapter One

Radioactive material or elements are substances or elements that emit radiation, such as Cesium-137. This corresponds to wood which can serve as fuel for a bonfire. Radioactivity is the ability of a radioactive substance to emit radiation. This corresponds to a bonfire's heat. Thermal rays (i.e. radiation) can cause burns (i.e. radiation injuries), and the burns (i.e. radiation injuries) will be proportional to the bonfire’s heat power (i.e. radioactivity). The term radioactivity is used to describe the ability to emit radiation, and this is independent of the type of radiation. Also, this term is used to describe radiation from naturally radioactive materials, but not from radiation generators such as X-ray tubes.

1.1.2 Different types of radiation and their penetration abilities

Currently several types of radiation, including α-rays, β-rays, γ-rays and X-rays are known. To understand their properties, a review of the structure of atoms is necessary. In an atom, a negatively charged electron is orbiting around a positively charged nucleus. This electron is referred to as an orbital electron (Fig. 1.4) because can only be present in defined atomic which are described as the K shell, L shell, M shell, N shell, O shell, and P shell. The orbits get larger with each of the sequential letters used to name the orbits. The electrons of the outermost shell are associated with the chemical nature of the atom. For example, Na, K, and Cs belonging to the same congener (alkali metals) in the periodic table, and have only one electron in the outermost M shell, N shell, or P shell, respectively. When these electrons are free or released from the atom, these atoms become positive mono-valent ions, such as Na+, K+, Cs+. The strength of the positive charge in the nucleus is determined by the number of present in the nucleus, so that the proton number for the atom always coincides with the number of orbital electrons unless the atom is ionized (i.e. loses an electron). As the number of protons increases, the atom’s size increases, and there is an increase in the number of outermost electrons. The number of protons will define the physical nature of the atom. Thus, the number of protons is the atomic number which represents the atom. The present in the nucleus have almost the same as the protons, and the total number of protons and neutrons is called the mass number. The atomic number and mass number are expressed as the "mass number (upper row) / atomic number (lower row) and atom name" (Fig. 1.4). For example, cesium present in the 133 environment is represented by 55 Cs where 133 is the mass number and 55 134 is the atomic number. Similarly, radioactive cesium is designated as 55 Cs The Nature of Radiation 7

137 and 55 Cs. Although these cesium forms have different mass numbers, such as 133, 134, 137, the atomic numbers are all 55, indicating that they are all the same element cesium. Conventionally, the atomic number 55 is often omitted. When atoms have the same number of protons but different mass numbers, they are called , and are described by terms such as Cesium-137. When isotopes are radioactive, such as Cesium-134 and -137, they are called radioisotopes. Conversely, nonradioactive isotopes, such as Cesium-133, are called stable isotopes.

Mass number (protons + neutrons)

137 55Cs Element symbol Nucleus Atomic number (Numer of protons) 55 protons K shell 82 neutrons 55 electrons L shell (M, N, O shells) P shell

Figure 1.4 Nuclear model of Cesium-137. The nucleus of a Cesium-137 atom consists of 55 protons, 82 neutrons and 55 orbital electrons, including 1 electron in the outermost P shell.

When protons and electrons or nuclei are accelerated to a high speed, they behave as radiation. The α-rays discovered by Rutherford were high- speed helium nuclei. The helium nucleus is a large particle composed of two protons and two neutrons. Thus, the helium nucleus is bulky in terms of size and charge, so a helium atom α-ray interacts frequently with a nucleus in target substances and loses all its energy in a short distance. For this reason, an α-ray cannot penetrate human skin and is easily shielded by a piece of paper (Fig. 1.2). On the other hand, β-rays are high-speed electrons. An electron is one of the elementary particles which are the components of an atom, and its mass is about 1/1800 of a proton. Since electrons are much smaller than helium nuclei, they can penetrate matter much more effectively than α-rays. For that reason, β-rays can require 8 Chapter One several mm of aluminum foil to shield a target (Fig. 1.2). However, β-rays cannot reach deeper parts of the body although they can penetrate human skin. Neutrons and proton particles accelerated to a high velocity are called neutron beams and proton beams, respectively. Like α-rays and β- rays, neutron beams and proton beams are generally called particle beams. When radionuclides decay through the emission of α-rays or β-rays, additional energy remaining in the nucleus can be released as γ-rays. γ- rays are electromagnetic waves, like light and ultraviolet light rays, but they have a tremendous amount of energy. They can cause ionization by ejecting orbital electrons in atoms when they interact with matter. Thus, γ- rays originate during the decay of a nucleus, whereas X-rays are produced by electrons originating outside of the nucleus, but they are both electromagnetic waves. When ionization occurs through the ejection of electrons in the inner orbits, electrons from the outer atomic orbits can occupy these vacant inner positions. The energy difference between inner orbit electrons and outer orbit electrons is released in the form of X- rays (Fig. 1.5a). This type of X-ray is called a “characteristic X-ray”, which has a corresponding to the differences in the orbital energies in a specific atom (Fig. 1.5b). However, the X-rays originally observed by Roentgen were X-rays which are generated through a different mechanism than characteristic X-rays (Fig. 1.5a). When electrons are released from the high voltage cathode in a Crookes tube, they are pulled to the positively charged nuclei of the molecules which compose the glass tube, and are decelerated by a braking mechanism (bremsstrahlung). These decelerated electrons have a reduced kinetic energy and emit their lost energy as electromagnetic waves (i.e. as bremsstrahlung X-rays). Unlike characteristic X-rays, bremsstrahlung X-rays are characterized by a continuous energy distribution (Fig. 1.5b). Although X-rays generated from a Crookes tube are only bremsstrahlung X-rays, both characteristic X-rays and bremsstrahlung X-rays are generated from high voltage X-ray generators like the Coolidge tube currently in use. There are essentially no differences in the physical properties between X-rays (characteristic X- rays and bremsstrahlung X-rays) and γ-rays except for the mechanism which generates them. Since both γ-rays and X-rays are high energy electromagnetic waves, they have a much higher ability to penetrate matter than particle beams such as α-rays and β-rays, and are capable of penetrating the human body (Fig. 1.2).

The Nature of Radiation 9

(a) X-ray generation (b) Energy distribution

Characteristic X-rays Characteristic X-rays

Bremsstrahlung X-rays Dose of X-rays

Bremsstrahlung 0 50 100 150 200 X-rays Electron X-ray energy (keV)

Figure 1.5 X-ray generation from electron collisions. X-rays generated by electrons colliding with matter are classified into two types of X-rays according to the mechanism involved: (a) Bremsstrahlung X-rays are generated by the deceleration of electrons, and characteristic X-rays are generated when external orbital electrons transit into an empty inner orbital position. (b) Bremsstrahlung X-rays show a continuous energy spectrum, but the energy of characteristic X-rays are called eigenvalues which correspond to the energy difference between the two electron orbits.

1.2 Mechanisms of ionization and radiation units 1.2.1 How radiation causes ionization

When radiation collides with or interacts with matter in its path, it can gradually lose energy and eventually dissipate. During this process, the radiation can cause ionization and excitation events in the molecules it interacts with, although the detailed aspects of ionization differ between electromagnetic waves and particle beams. Since all radiation damage to the human body originates from these ionization events, a more detailed examination of these events is warranted. The processes through which electromagnetic waves such as X-rays and γ-rays lose energy in matter are classified into three types: the , , and electron pair production. In the photoelectric effect an X-ray or γ-ray interacts with matter, causes the release of orbital electrons in an atom (thus generating ionization events), and is completely absorbed (photoelectric absorption). The amount of X- ray and γ-ray energy expended during the ionization action is usually 5 to 30 eV (electron ), and the remainder of the energy provides the kinetic energy of the emitted electrons (called photoelectrons). An eV 10 Chapter One

(electron ) is a very energy unit used to describe the energy present in atoms and electrons (1 eV = 1.60 × 10-19 ). One eV is defined as the amount of energy given to one electron with a voltage of 1 V (volt). For example, the electron energy generated in an X-ray tube with a voltage of 1000 V is 1.0 keV (or kilo-eV). The energy at which the photoelectric effect occurs varies with the material. For example, the energy of X-rays and γ-rays at which the photoelectric effect occurs with aluminum or lead is 50 keV and 500 keV, respectively. In the photoelectric effect, the radiation itself is absorbed. X-rays and γ-rays with higher energies, such as 50 keV or more in aluminum, can cause ionization, although the energy will not be entirely delivered to the electrons. After the first interaction, X-rays and γ-rays will have lost some energy, but are still able to undergo subsequent secondary interactions with other atoms, causing sequential ionization events (Compton scattering). Electrons generated during these events are called Compton electrons (Fig. 1.6a). As the energy diminishes during this Compton scattering process, the photoelectric effect will finally take place and the radiation’s energy will be fully absorbed. Electrons (both photoelectrons and Compton electrons) generated by the photoelectric effect and Compton scattering will continue to collide with other atoms, so that the chain of events can describe a complex pattern. In addition to ionization, fluorescence is also emitted through the excitation of atoms during this process. This is the fluorescence Roentgen observed in a substance placed at a distance from his X-ray tube.

Figure 1.6 Ionizing mechanisms and their ranges. (a) γ-rays gradually lose energy while penetrating matter and undergoing ionizing events, such as electron pair production, and Compton scattering or the photoelectric effect. α-rays and heavy particle beams follow a straight path and The Nature of Radiation 11 cause ionization, and are finally absorbed by losing their energies in the material they are traversing. β-rays also undergo repeated collisions and cause ionization while generating bremsstrahlung X-rays. (b) Radiation usually will not travel completely through a target, and will be absorbed when it loses all of its energy. α- rays and β-rays gradually lose their energy, while heavy particle beams stop at a certain specific distance from the surface of the skin forming a Bragg peak.

High energy γ-rays with energies over 1.02 MeV (mega-electron volts or one million electron volts) can produce both, negatively charged electrons and positively charged , in the vicinity of the nucleus simultaneously, and this is described as electron pair production. Since the positron is unstable, it immediately decays, emitting two γ-rays with energies of 0.51 MeV (i.e. annihilation radiation) (Fig. 1.6a). The absorption of radiation energy during these processes tends to increase as the atomic number of the target substance increases. For this reason, lead or elements with a high atomic number are usually used for shielding from X-rays and γ-rays (Fig. 1.2). Particle beams, such as α-rays and β-rays, collide with atoms and cause ionization and excitation. Repeated subsequent interactions with additional atoms weakens or to the absorption of their radiation energy. During this process, particles with small , such as β-rays, can have their path altered or bent by the electric field of the nucleus, and generate bremsstrahlung X-rays, and gradually lose energy (see above). Conversely, particles with large masses, like α-rays, travel linearly along their path, so that the generation of bremsstrahlung X-rays is usually not significant (Fig. 1.6a). A high velocity beam of particles which have an atomic number larger than helium is called a heavy particle beam, for example a beam composed of ions. Heavy particle beams cause high density ionization tracks to form along their paths and quickly lose all of their energy. Consequently, heavy particle beams stop after a constant distance, and the ion density along their track reaches a notable maximum near the end of the track (this is called the Bragg effect and is illustrated in Fig. 1.6b). In contrast to heavy particle beams, β-rays are gradually attenuated along their path during their penetration of a target, so their ionization track is gentle and uniform when compared to the ionization tracks of heavy particle beams (Fig. 1.6b). In neutron beams, the neutrons have no charge, and hence lose energy through collisions with nuclei rather than with orbital electrons. Since the mass of a hydrogen nucleus is the same as a neutron, the collision of a neutron with a hydrogen nucleus reduces its radiation energy most efficiently. Hence, water is appropriate for use as a neutron shield (see Chapter 2.2.2). 12 Chapter One

1.2.2 Radioactivity and radiation units

Various units are used to measure radiation and radioactivity, and the units which are used depends on what purpose these measurements are being used for. These measurements could be used to study radiation protection, , environmental decontamination, etc., and the amount of radiation and radioactivity present must be quantified. Although these units, in theory, represent the number of calories of radiation energy absorbed per unit weight and the weight of radioactive substances, respectively, specific defined units, such as the , or Becquerel, are most convenient to describe specific properties of radiation. These units were named after the physicists Louis H. Gray (UK), Rolf M. Sievert (Sweden), and Antoine H. Becquerel, all of whom made important contributions in the early history of radiation research. The Gray is a unit used to define the amount of radiation absorbed (the ) when 1 (J) of energy is absorbed per kg of substance, and this measure can be used in the study of living organisms. The Gray is represented by the symbol Gy (Table 1.1). One hundredth of a Gray or a cGy (centi-gray) can be used as a convenient unit, because it is easy to convert the cGy unit to a in the CGS unit system which was used in biological research papers before the Gy became widely used (1 rad = 1 cGy). Even when various targets are exposed to the same absorbed dose in Gy, the biological effects of radiation can still be different depending on the specific type of radiation which is incident, and the specific tissues or organs which receive the radiation. The and effective dose are calculated by multiplying the dose in Gy by specific coefficients, and these doses are used in working with radiation protection. A Sievert is used for both the equivalent dose and effective dose, and is represented by the symbol Sv. The relationship between the equivalent dose (Sv) and the Gray (Gy) is:

Equivalent dose (1 Sv) = 1 Gy × Wr where Wr is a radiation weighting factor. The radiation weighting factor Wr is a coefficient which is determined by the type of radiation involved. For example, Wr is 1.0 is for γ-rays and β-rays, and 20 for α-rays. Other energy-dependent coefficients are used for neutron beams whose quality can vary with the neutron energy (Table 1.1). Since the radiation weighting factors for γ-rays and β-rays are 1, the absorbed doses in Gy have the same numerical values as the equivalent doses in Sv. The Nature of Radiation 13

Unit Definition Purpose Radiation A unit of an absorbed radiation This unit is used in basic dose dose when 1 kg absorbs an physical studies, biological Gy (Gray) energy of 1 Joule (about 0.24 experiments and radiation calorie) therapy. Sv (Sievert) Radiation dose unit representing This unit is used in describing radiation effects in humans. radiation protection and in Equivalent The dose in Gray is multiplied evaluating radiation effects on dose by a radiation weighting factor the human body which vary Wr (Gy × Wr). Wr values for X- with the type of radiation. rays, γ-rays, and β-rays are all 1. Wr values are 20 for α-rays, respectively. Effective The sum of the total of the doses This unit is used for legal dose delivered to specific tissue regulations and in radiological targets. This dose is multiplied protection to provide an by a tissue weighting factor Wt evaluation of the radiation’s for each tissue. Wt values for effect on the whole body specific tissues are 0.12, 0.08 when only a specific tissue is and 0.01 for bone marrow, exposed. gonads and skin, respectively. Radioactivity The number of atomic decay per The Becquerel is the product of Bq . the decay rate and the number (Becquerel) of atoms, so it is proportional to the amount of a radioactive substance which is present. Quality of The amount of energy (keV/µm) α-rays and heavy that is transferred to a target beams that produce dense when the radiation traverses a ionization have a high LET LET (Linear unit distance. The LET value is value, and lead to large energy 0.2-2.0 keV/µm for Cobalt 60 γ- biological effects, while X- transfer) rays and X-rays, and 110 rays and β-rays with low LET keV/µm for 4 MeV α-rays. values produce smaller effects Table 1.1 Units used for radiation

The equivalent dose × Wt is calculated for each tissue, and the sum of all of the individual doses to each of the exposed tissues is the effective dose:

Effective dose (in Sv) = Σ (sum of equivalent tissue doses ×Wt)

Where Wt is a tissue weighting factor for each tissue and Σ is the sum of the individual equivalent doses delivered to each tissue. 14 Chapter One

The dose unit used for writing legal regulations or for writing laws is the effective dose, which is the equivalent dose multiplied by the tissue weighting factor Wt. The tissue weighting factor is a coefficient obtained by apportioning the radiation risk for each tissue in order to evaluate the effect of radiation on the whole body when a specific tissue is exposed (Table 1.1). For example, the specific Wt factors are 0.01 and 0.12, for skin and bone marrow, respectively. The total sum of the individual tissue weighting factors for each tissue adds up to 1 for the entire organism. Since both the equivalent dose and the effective dose are described by the Sievert or Sv unit, it is necessary to pay attention to precisely which dose is referred to when the dose is described in (Sv). Small doses can be described using mSv or millisieverts which correspond to 1/1000th of a Sievert, and in microsieverts (µSv) which correspond to 1/1,000,000 of a Sievert. In addition, the dose delivered in a unit of time, such as an or minute, is described by the dose rate and is expressed in µSv/hr or µSv/min. For example, if one is exposed for 8 a to a dose rate of 10 µSv/hr, the total dose is caluculated as 10 µSv/hour × 8 hours × 365 days = 29.2 mSv in one year. However, a practical effective dose description which is used in radiation protection work is the 1 cm dose equivalent (in Sv) which is used to describe the dose at a depth of 1 cm below the body’s surface (where the exposure is maximum) when discussing exposures to X-rays or γ-rays. Because the 1 cm dose equivalent always has a value higher than the equivalent dose and provides a conservative (if slightly overestimated) radiation exposure estimate, radiation dosimeters (e.g. survey meters) indicate the 1 cm dose equivalents. Because the Gy describes the energy absorbed per unit weight, a conversion to calories is plausible. For example, half of the people irradiated with 4 Gy (= 4 J/kg) in a whole body exposure will die within 60 days (see Chapter 5.3.1), but the total thermal energy absorbed by the whole body (60 kg) is

4 (J/kg) x 60 (kg) = 240 (J) = 57.6 (Cal)

57.6 Cal (calories) can lead to an increase in body temperature of merely 0.00096°C, and this is the same effect one would see from drinking a small spoon full (2.5 ml) of hot water (60°C). Consequently, although the absorbed caloric radiation energy is negligible, there is a still a sufficient amount of energy to ionize and subsequently cleave molecular bonds in any region along the radiation track (path).