Radiation Biophysics

492 Pages·1998·24.09 MB·English

by  Edward L. Alpen

Preface to the Second Edition
The driving force for my undertaking a revision of this text has been the
comments of my colleagues and others about the need for change in
emphasis or additions that would better fulfill their pedagogical goals. I
was pleasantly surprised to find that the field of radiation biophysics has
made tremendous strides in the past 6 years. I have, of course, been aware
of progress, but only when one sits down and organizes all the changes that
are necessary does one appreciate the overall magnitude of change. I
originally undertook the creation of the first edition to carry on a tradition
established by H. L. Andrews, the author of the original text, Radiation
Biophysics. These purposes are well set forth in my preface to the first
edition: to approach the subject with mathematical rigor, but not to the
extent that the biologist would be afraid to enter.
Some of the changes added at the request of colleagues include a brief
description of acute radiation syndrome in human beings, expansion of the
sections on neutron interactions in tissue, and the expansion of the
chapters on high LET effects and cancer.
Many changes have been made to keep up with new findings. This si
particularly true in radiation chemistry of macromolecules and transforma-
tion systems for cells irradiated in vitro.
SI units are now used throughout, and the only references to rad and
rem are in tables or figures generated and published by others.
Finally, I thank several of my colleagues who willingly critiqued the
various chapters, and I also thank the authors who kindly consented to my
use of their published illustrations.
Edward L. Alpen
xxiii
Preface to the First Edition
The contents of this text are the result of particularly frustrating
experiences for me while teaching a senior course in radiation biophysics
at Berkeley. The students in the course are, in general, majors in bio-
physics or medical physics who have quite sophisticated training in the
physical sciences and mathematics, as well as more than adequate skills in
biology. In choosing a course text it was necessary to propose to them
several volumes, only parts of which would ultimately be used in the
course. The choices among texts currently offered are those which are best
suited to training radiation diagnostic and therapy physicists, which em-
phasize the physical interactions of radiation with matter with only a polite
nod to the biology and chemistry of radiation interactions; or the radiation
biology texts, which, with only infrequent exceptions, assume that a biolo-
gist has never seen a differential equation.
It is rare today to find undergraduate majors in biology that have not
had fairly sophisticated "cross-training" in mathematics and the physical
sciences. It is also true that many of the undergraduates in the physical
sciences would like to increase their knowledge of the interaction of
physical agents with living systems without being affronted by the lack of
quantitative approach to the biology. In a sense, this cross-disciplinary
curiosity has been the driving force behind the development of that
modern discipline, biophysics. It would be naive of me, however, to assume
that all potential users would have the necessary physical science back-
ground for the material of the text, and wherever I have felt it necessary,
fundamental material at the beginner level is included.
My aim has been to produce a text that would be useful for advanced
undergraduates and graduate students in the appropriate sciences, while at
the same time filling a need for a desk-top reference for working scientists
in the field. The book should prove useful for health physics students and
working professionals, for those engaged in the radiological sciences in the
XXV
xxvi ecaferP ot the First Edition
health professions, and for individuals in related fields such as nuclear
power generation and federal and state regulatory activities.
The book is structured for a 16-week, one-semester course. It pro-
gresses from the physical interactions to the radiochemical interactions to
the biological sequelae. Finally, it deals with the late effects of ionizing
radiation on organized living systems, in particular, human beings. Those
who use this text will find that they can devote as much or as little time to
the physical science chapters as they wish. The biology is pretty much
intact on its own.
Chapter 2, the electromagnetic spectrum and the properties of radia-
tion, is essential for all readers who have not had adequate training in
electromagnetic radiation and its characteristics. Those who have can
easily skip this material. Chapter 5 on energy absorption mechanisms is
quite helpful background for all readers, a review for some and new for
others.
I have strived for correctness in all parts of the volume, of course, but
particularly in the physical science chapters. It will, I hope, be found that
the presentation is rigorous. This presentation will not be entirely com-
plete, however. There has been no effort to present complete derivations
of some of the more complicated formulations. The Bethe-Bloch stopping
power equation, the Klein-Nishina Compton cross-section calculations,
and the Compton scatter energy transfer formulations are examples of
these. The final formulation is complete, but the reader is referred
elsewhere for complete derivations.
The text has, insofar as possible, used classical Newtonian mechanics to
explain physical principles. At times, where relativistic corrections or other
quantum mechanical treatments are required, they are given without
derivation.
The background expected of the student to effectively utilize this text is
mathematics through a first course in differential equations, a good lower-
division physics course, including introductory quantum mechanics, organic
and/or biological chemistry, and a simple knowledge of cell biology.
Finally, I express my heartfelt thanks to all of my many colleagues and
friends who have so helpfully reviewed various chapters and sections of the
book.
Edward L. Alpen
Introduction:
An Historical Perspective
The technological and medical applications of radiation and radioactiv-
ity have become so much a part of our everyday life that it is easy to lose
sight of the fact that all of radiation science is recent by our usual view of
historical calendars. In 1995, the world of radiological science celebrated
the centenary of R6ntgen's announcement of the discovery of a "new kind
of penetrating ray." The history of the next few months after that an-
nouncement is so dramatic, including Becquerel's discovery of natural
radioactivity, that it is worth recounting if for no other reason than to
reassure us that, at times, science does indeed make giant strides in a brief
period.
Unfortunately, knowledge of the biological effects of ionizing radiation
and radioactivity lay unexplored for several decades after R6ntgen's initial
report. A number of early pioneers in the separation and use of radio-
active materials suffered significant adverse medical effects from their
exposure.
During 1895, R6ntgen was carrying out experiments with electrical
discharge in evacuated glass tubes (Crooke's tubes) and he noticed that
photographic plates lying near his experimental apparatus showed signifi-
cant darkening when they were subsequently developed. This story is well
known, but the further impact of his announcement is not nearly as well
recognized. On December 28, 1895, R6ntgen reported before the Wiirz-
burg Philosophical Society his observation that he had discovered a pene-
trating ray that would darken photographic plates (R6ntgen, 1895). Shortly
after his Wiirzburg report was presented, he sent copies of the report,
along with samples of what he called X-ray photographs, to the leading
physicists in Europe.
xxvii
xxviii Introduction
On January ,02 1896, two French physicians, Oudin and Barth61emy,
submitted an X-ray photograph of the bones of the hand before the
Acad4mie Fran~aise. At the same meeting, Henri Poincar4 reported on
the paper he had received from R/Sntgen. Henri Becquerel was present,
and, since he was actively working on fluorescence, he doubted that
R/Sntgen had discovered a new "ray"; he was convinced that in some way
the fluorescence produced in the glass wall of R/Sntgen's Crooke's tube was
responsible for the darkening of the photographic plates. What then
followed is most remarkable for the intensity of effort and the insight
shown by Becquerel. He published the first of four papers (Becquerel,
1896a-d), presented before the Academy on February ,42 1896, that
remarked on the relationship of "phosphorescence" and the penetrating
rays. On May ,81 1896, he presented the fourth in the series, titled
"Emission of New Radiations by Metallic Uranium," in which he lay claim
to discovery of what eventually came to be known as natural radioactivity.
Only 21 weeks elapsed from the first concept to the final conclusion
(Becquerel, 1896d)! One cannot help but observe that in our time it is
unlikely that a paper could even be reviewed in 21 weeks, let alone be
published.
American scientists had not let R/Sntgen's discovery go unnoticed. Two
individuals, Michael Pupin, a physicist at Columbia University, and Thomas
Alva Edison, were racing to be the first on this continent to report findings
with the new "invisible rays." The race was won by Edison with a
publication in the yrutneC detartsullI enizagaM on February ,1 1896--only
two months after the Wiirzburg announcement.
Edison went on to become a major force in the commercialization of
X-ray equipment for medical applications, and it is no accident that
General Electric Corporation was an early leader in the marketing of
medical X-ray equipment. One of Edison's great contributions to medical
radiology, which is often overlooked, was the invention of the fluoroscope.
With his usual intensity, Edison paid little heed to the potential hazards of
X-rays, and his assistants in particular suffered the consequences. The
following quotation is from his biography (Dyer, Martin, and Meadowcroft,
.)9291
When the x-ray came up, I made the first fluoroscope, using tungstate of
calcium. I also found that this tungstate could be put into a vacuum chamber of
glass and fused to the inner walls of the chamber: and if the x-ray electrodes
were let into the glass chamber and a proper vacuum was attained, you could
get a fluorescent lamp of several candlepower. I started in to make a number of
these lamps, but I soon found that the x-ray had affected poisonously my
assistant, Mr. Dally, so that his hair came out and his flesh commenced to
An Historical Perspective xxix
ulcerate. I then concluded it would not do, and that it would not be a very
popular kind of light; so I dropped it.
The applications for X-rays in medicine were so obvious that there was
no stopping this new technology. The first medical X-ray was made in 1896.
History was made in military medicine when portable X-ray machines were
deployed with Kitchener's Army of the Sudan in 1898 and were used
routinely for diagnostic assistance in traumatic injury. In 1898 the Medical
Record (New York) carried 28 references on radiological diagnoses and
procedures.
Becquerel was disgruntled and disappointed for some years that his
discovery of natural radioactivity received few accolades and even less
attention. He proceeded with his work, however, and did demonstrate that
the rays from uranium would ionize gases (Becquerel, 1896d). There is a
story, which I must label apocryphal since I can find no reliable record of
it, that he carried a small vial of the newly discovered radium in his
waistcoat pocket, and he used this radioactive sample to demonstrate that
the rays would discharge a gold-leaf electroscope. It also has been re-
ported that he later suffered radiation damage to the skin of his abdomen
from this practice, but, again, this fact cannot be reliably confirmed. In any
case, J. J. Thomson, the distinguished English physicist, formed an associa-
tion with a young New Zealander, Ernest Rutherford, and, together, in
1896, they reported on the ionizing properties of X-rays (Thomson and
Rutherford, 1896). This early association between Thomson and Ruther-
ford initiated the latter into the mysteries of the newly discovered radioac-
tivity and radiations, and these studies formed the basis for his life's work.
Rutherford, in association with Owen and others at McGill University
in Montreal, made a series of discoveries that became central to the future
of radiation science. Among these discoveries was the demonstration that
the radiations from naturally occurring sources were made up of three
different types of rays: a penetrating ray of great mass that was deflected
in an electric field (alpha ray), a second penetrating ray of lesser mass
(beta ray) that was also deflected by an electric field, and, finally, a ray that
was unaffected by an electric field (gamma ray). His other contributions
are known mostly to students of the physical sciences, but probably less
well known is the fact that he and Owen were the first to demonstrate the
existence of gaseous matter arising from thorium that could itself be
radioactive (Rutherford, 1900). This gas was thoron. The discovery of
thoron and its properties was a demonstration, for the first time, of the
chain decay of radioactive elements.
For all of Rutherford's vision, he was not infallible. To quote from a
speech he made in 1933 before the British Association for the Advance-
xxx Introduction
ment of Science:
The energy produced by the breaking down of the atom is a very poor kind
of thing. Anyone who expects a source of power from the transformation of
these atoms is talking moonshine.
One of the key chapters in the early history of radiation science must,
of course, be the discovery of radium by Pierre and Marie Curie and the
discovery of polonium by Marie after the death of her husband, Pierre. It
would be romantic fiction to assume that Pierre Curie fell victim to the
dangerous rays of the substance that he discovered in collaboration with
his wife; he was simply the victim of a carriage accident in the streets of
Paris. It ,si however, indeed true that both Marie and her daughter were
victims of their discoveries. Both died of leukemia, which must certainly
have been caused by their exposures during the isolation of radium and
polonium.
The time from R6ntgen's announcement of the discovery of X-rays until
Rutherford's (Rutherford and Soddy, 1903) classic paper, which described
the transitions among the elements of the natural radioactive series,
encompasses only the years from 1895 to 1903mless than a decade. This
latter paper of Rutherford's was, in a sense, the realization of an old
dream of chemists because it represented transmutation of one element to
another. The impact of Rutherford's paper on our understanding of
natural radioactive chains si hard to overstate. In this text, the chapter on
serial radioactive decay still uses the notation and formulation set out by
Rutherford for the description of decay in a radioactive series as described
in his 1903 report.
What about the biology of radiation? What was being done to examine
the biological effects of these new rays? Next to nothing except by sad
accident. Pierre Curie carried out a few small experiments on the biologi-
cal effects of the emanations from radium. In particular, he reported
before the Acad6mie Franqaise on his studies on the effects of radium
emanations on developing tadpoles. He found that these emanations
produced severe developmental abnormalities in the growing tadpoles.
Little attention was paid to these findings, and even when early radiolo-
gists developed skin lesions and lost fingers there was little attempt to
systematically examine the effects of radiation on living systems.
In 1902 it was first formally reported that radiation of the skin with
X-rays could lead to skin cancer, but even then, few scientists were
motivated to proceed with studies of the systematic biology of radiation.
The first truly systematic study of the pathological effects of ionizing
radiations on animal systems was done by Heineke (Heineke, 1905), whose
studies reported on mice, guinea pigs, rabbits, and dogs. Special attention
An Historical Perspective xxxi
was paid to the reproductive systems of irradiated rodents by Albers-
Sch6nberg (1903) and by Halberst~idter (1905). Bergonie and Tribondeau
(1906), after extensive studies of the testes of rodents, formulated what has
come to be known as the "Law of Bergonie and Tribondeau." Remarkably,
their statement of some principles of radiation effects on cells remains
sound today, with some important exceptions. They stated that if cells have
a high mitotic rate, that under normal circumstances they will undergo
many mitoses, and that they are generally of a "primitive" type, then they
will be radiosensitive. We can identify many exceptions at this time, but
the core meaning of the rule remains useful.
Radiation biophysics as a quantitative science saw the light of day in the
1920s with Dessauer's (1922) efforts to quantitatively investigate the ef-
fects of radiation. These early studies were centered around a statistical
analysis of dose-response curves in an effort to understand the mecha-
nisms of radiation action. Except for the truly insightful studies on the
mutagenic action of ionizing radiation, by Mfiller in 1927 (reviewed in
Mfiller, 1950), little else happened before World War II.
One of the great constraints on the biological investigation of radiation
effects in these early times lay in the limited ability to quantitate dose. In
the immediate postwar years, due in part to the atom bomb and its impact,
radiation biology and biophysics came into its own with the work of
pioneers such as Lea and his colleague Catchside, as well as the work
of the German biophysicist Zimmer. It is interesting to observe that most
of the early workers in this field were physicists who turned to biology,
perhaps because their biological colleagues were slow to enter this difficult
field.
The event that probably had the most significant impact on modern
radiation biophysics was the publication of a new method for the quantita-
tive culture of mammalian cells by Puck and Marcus (1955). Until this time
all radiation experiments that involved analysis of survival data had to be
carried out on prokaryotic cells or yeast. Now, for the first time, target
theory, statistical killing models, and repair-recovery mechanisms could be
evaluated and analyzed on mammalian cell lines. The enormous impact of
this new methodology can be measured by examining Chapter 8 of this
text. In particular, the proposal of a model for repair of sublethal damage
by Elkind and Sutton (1960) revolutionized our thinking about the initial
injury to DNA and the subsequent complicated repair processes.
We are now on the verge of a new cycle of significant discoveries
related to the effects of ionizing radiation. Progress in the molecular
biology of DNA is providing new tools almost daily for the examination of
damage and repair processes in this important biomolecule. If we reexam-
ine the field of radiation bioeffects a decade from now, we may find that
xxxii Introduction
this decade is in many ways similar to the 1895-1905 period, which was the
"golden age" of discovery for radiation and radioactivity research.
REFERENCES
Albers-Sch6nberg, H. E. (1903). Uber eine bisher unbekannte Wirkung der R6ntgenstrahlen
auf der Organismus der Tiere. Munch. Med. Wochenschr. 50, 1859-1860.
Becquerel, H. (1896a). On the radiation emitted in phosphorescence. C. R. Acad. Sci. Paris
122, 420-421 (24 February).
Becquerel, H. (1896b). On the invisible radiations emitted by phosphorescent substances.
C. R. Acad. Sci. Paris 122, 501-503 (2 March).
Becquerel, H. (1896c). On the invisible radiations emitted by the salts of uranium. C. R.
Acad. Sci., Paris 122, 689-694 (23 March).
Becquerel, H. (1896d). Emission of new radiations by metallic uranium. C. R. Acad. Sci.
Paris 122, 1086-1088 (18 May).
Bergonie, J., and Tribondeau, L. (1906). Action des rayons X sur le testicule. Arch. Elect.
Med. ,41 779-927.
Dessauer, F. (1922). Uber einige Wirkungen von Strahlen, I. Z. Phys. ,21 38-44.
Dyer, F. L., Martin, T. C., and Meadowcroft, W. H. (1929). Edison, His Life and Inventions,
pp. 580-583. Harper, New York.
Elkind, M. M., and Sutton, H. (1960). Radiation response of mammalian cells grown in
culture. I. Repair of x-ray damage in surviving Chinese hamster cells. Radiation Res. ,31
556-593.
Halberst~idter, L. (1905). Die Einwirkung der R/Sntgenstrahlen auf Ovarien. Klin. Wochen.
Berlin 42, 64-66.
Heineke, H. (1905). Experimentelle Untersuchungen fiber die Einwirkung de R/Sntgenstrah-
len auf innere Organe. Mitt. Grenzg. Med. Chir. ,41 21-94.
Miiller, H. J. (1950). Radiation damage to the genetic material: I. Effects manifested mainly
in the descendants. Am. Scientist 38, 33-40.
Puck, T. T., and Marcus, P. I. (1955). A rapid method for viable cell titration and clone
production with HeLa cells in tissue culture: the use of x-irradiated cells to supply
conditioning factors. Proc. Nat. Acad. Sci. U.S.A. 41, 432-437.
R6ntgen, W. C. (1895). On a new kind of rays. Sitzgsber. Physik-Med. Ges., Wiirzburg 137 also
Ann. Phys. Chem. N.F. 64, 1 (1898).
Rutherford, E. (1900). A radioactive substance emitted from thorium compounds. Lond.
Edin. Dublin Phil. Mag. J. Sci. 49, 1-14.
Rutherford, E., and Soddy, F. (1903). Radioactive change. Lond. Edin. Dublin Phil. Mag. J.
Sci. 52, 576-591.
Thomson, J. J., and Rutherford, E. (1896). On the passage of electricity through gases
exposed to R/Sntgen rays. Phil. Mag. 42, 392-407.
SUGGESTED ADDITIONAL READING
Glasser, O. (1958). Dr. W. C. R6ntgen, 2nd ed. Charles C. Thomas, Springfield, IL.
Romer, A., Ed. (1964). The Discovery of Radioactivity and Transmutation, Classics of Science,
Vol. II. Dover, New York.
Zimmer, K. G. (1961). Studies on Quantitative Radiation Biology, Oliver and Boyd, Edinburgh.
Chapter 1
Quantities, Units,
and Definitions
QUANTITIES AND UNITS
Every specialized field of human endeavor that requires quantitation in
its pursuit must establish meaningful descriptions of whatever property or
quantity si being measured. Radiation science and radiation biophysics are
no exception to this rule. This field si no exception to another general rule:
each discipline tends to create a set of its own units, with special defini-
tions. As disciplinary studies tend to expand and overlap with other
specialities, conflicts arise among the specially developed units and quanti-
ties that each field has invented. In 1974 the International Committee for
Weights and Measures (Comit4 Internationale des Poids et M4sures)
undertook a rationalization of the descriptions of all quantities and units
in use in science and attempted to minimize the "special" quantities and
units that had proliferated over the years. The new units, described by the
abbreviation "SI" for Syst~me Internationale, have been introduced in
most countries of the world (see, for example, National Bureau of
Standards, 1977).
Needless to say, there has been a good deal of resistance to the use of
SI units. One reason for resistance was the abandonment of old unit
names that stirred up nationalistic pride and chauvinism, such as replacing
the gauss with the tesla as the unit of magnetic field strength and replacing
the dyne with the newton as the unit of force. Another operationally
important factor that delayed implementation of the SI system was the
cumbersome size of some of the new units; some were too tiny and some
were too large.