RADIATION INJURies by mrsurgeon

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									                            RADIATION INJURY STUART C. FINCH
       Throughout life human beings are continuously exposed to many types of radiation,
some harmless and some harmful. The most harmful is ionizing radiation, which damages
tissue through the action of charged particles. More is known about the acute and late
somatic teratogenic, and genetic effects of ionizing radiation than about any other
environmental, physical, or chemical agent or force, yet many gaps remain in our knowlege
concerning its effects. Most important and least well understood are the late effects of
chronic low-dose radiation expousure. There is little reliable direct information, based on
studies for which there are'good quantitative rediation dose estimates and high statisticacal
power, so virtually all ectimates of low-high-dose exposure results.
       There are two types of ionizing radiation. The first con- sist of high-frequency
electromagnetic waves of relatively short wavelength, such as naturally occurring gamma
rays or machine-made x-rays. These waves are capable of deep tissue penetration and
moderate ionization of the tissues along their pathways by indirect mechanisms. There
interactions with the atoms and molecules of tissue structures result in the release of orbital
electrons and the formation of ions and reactive radicals that damage cell components and
disrupt biologic processes. The second type of ionizing radiation consist of a variety of
subatomic particles, protons, electrons, and electrically uncharged neutrons. The charged
particles densely ionize structures along their pathways in tissues. The depth of penetration is
quite limited and varies as a function of mass, charge, and velocity. Tissue damage is due to
the direct ionization of water, oxygen, and other molecules with the formation of free
hydroxyl radicals and highly reactive oxygen species. Neutrons penetrate tissue much more
deeply than charged particles of equivalent size (such as protons). They indirectly ionize
through their interactions with the nuclei of atoms, resulting in the release of protons, alpha
particles, and other nuclear fragments that damage other tissues.
       The longer-wavelength waves of the electromagnetic spectrum do not ionize, but
some may damage tissues by other mechanisms. For example, ultraviolet light penetrates
very little, but repeated acute exposures induce photochemical cellular damage that is
cumulative and irreversible, predisposing the development of melanomas, basal cell cancers,
altered cell-mediated immunity, and other systemic effects. Infrared, radio, and microwave
electromagnetic waves are capable of deep tissue penetration with the generation of heat, the
effects of which are largely reversible. Weak, low frequency electromagnetic waves have
been shown to modulate ion flow and to interfere with both RNA transcription and DNA
synthesis at the cellular level. Reports of increased leukemia, brain tumors, and other
neoplasms, especially in children, following prolonged exposure to various types of low-
frequency electromagnetic waves remain to be confirmed. The controversial medical effects
in humans of exposure to electromagnetic radiation are in sharp contrast to the
wellestablished acute and late effects of exposure to ionizing radiation, which is the only
subject considered in this chapter.
       TERMINOLOGY AND DEFINITIONS Some familiarity with radiation terminology
and units is essential for an understanding of the effects of ionizing radiation. An early term
for the quantitation of exposure was the roentgen (R), which represents the amount of radia-
tion-induced ionization in a standard volume of air. Much more important is the rad
(radiation absorbed dose), which represents a unit of absorbed ^ose in tissue. One rad
corresponds to the absorption of 100 ergs of energy(or about 1 R)in 1 g of tissue. Since the
same dose in rads of different kinds of ionizing radiation can produce different biologic
effects, the term rein (roentgen equivalent man)was introduced. It is the product of the rad
multiplied by its relative bioogic effectiveness(RBE), a factor that represents the biologic
potency of one type of radiation as compared wih another to produce the same biologic
effect. The usual standard of comparison used for the RBE is 200-kV x-rays, which are
similar in energy to gamma
       rays.Gamma radiation, therefore, has an RBE of about 1, and 1 rad of gamma
exposure is roughly equal to 1 rem. Neutrons and some charged particles may have an RBE
of 5 to 20 or greater. The terms gray (Gy), 1 unit of which is the equivalent of 100 rad, and
sievert(Sv), 1 unit of which is equal to 10Q_rem, have been adopted to replace the term rad
and rem, respectively. One-thousandth of a gray is written as 10 Gy or 1 mGy,equiva- lent to
0,1 rad (10 rad)or 100 millirad(100 mrad). Similarly, one-thousandth of a sievert is written as
10 or 1 mSv,equiva- lent to 0,1 rem (10 rem) or 100 millirem(100 mrem).
       The density of tissue ionization produced per unit length along the pathway of
ionizing radiation is expressed as its linear energy transfer(LET).In general, electrically
charged particles or particles of relatively high mass (alpha particles, protons, and neutrons)
have a high energy transfer (high LET), resulting in relatively large amounts of tissue
damage. In contrast, electromagnetic forms of ionizing radiation (gamma rays or x-rays) or
charged particles of small mass (electrons) transfer less energy per unit length of travel(have
low LET ) and produce less tissue damage. There is quite a good correlation between LET
and RBE.
       The threshold dose for a specific biologic effects is the minimum radiation dose that
will produce the effect. Radiation effects that vary in frequency with dose but not in severity
are called stochastic effects. Examples of these are radiation- induced carcinogenic,
mutagenic, and teratogenic effects. Nonstochastic effects vary in severity above a threshold
dose depending on the number of cells injured. Examples of such effects are radiation-
induced cataracts of the eye or fibrosis of the bone marrow. The interval of time between ex-
posure and the occurrence of a radiation effects is identified as its latent period. The maxi-
mum permissible dose is that dose of ionizing radiation which, in the light of present knowl-
edge, is not expected to cause any appreciable bodily injury to any person at any time during
a lifetime. Recommended annual limits by most U.S. radiation regulatory agencies for
absorbed whole-body radiation dose are 0,05 Sv for occupationally exposed persons and
0,001 Sv for the general public.
       TYPES AND SOURCES OF IONIZING RADIATION Most of a person s lifetime
radiation exposure is from low-dose background radiation. The average annual bakcground
dose for each person in the United States is quite variable but is estimated to be from 3 to 3.6
mSv. About 80 percent or four-fifths of this radiation is from natural sources, of which
radon, cosmic rays, radionuclides in the earth, and radioactive elements in the body are the
major contributors.
       Radon now is believed to contribute about half of a person's total bakcground
radiation exposure. The represents about 1.5 to 2 mSv of exposure per year. Radon is a
colorless, and tasteless alpha-particle-emitting radioactive gas which is derived from
naturally occurring uranium deposits in the earth. It seeps up through soil into the air, where
it and its decay products attach to dust, aerosols, or droplets that are inhaled and retained in
bronchial epithelium and adjacent structures. The greatest exposures occure in certain indoor
areas and mines where there are high adjacent rock concentrations of phosphates, granite,
and black shale. Radon itself is not particularly harmful, but some of its alpha-emitting
polonium radioactive decay product may heavily irradiatebronchial epithelial cells for many
months of years.
       Cosmic radiation accounts for about 0.3 mSv of background radiation per year at sea
level. It is composed of protons, neutrons, and heavy nuclei from galactic sources and low-
energy charged particles from the sun that interact with atmospherinc nuclei to produce small
secondary particlesand electrons that enter the body and ionize tissue. The earth's atmosphere
acts as a shield so th^t the dose is about doubled with every 1500 m of increase m altitude.
Radioactive potassium and carbon and other radionuclides within the body contribute about
another 0.3 to 0.4 mSv to the average person's annual background radiation exposure. Radio-
active decay of thorium and uranium radionuclides in the earth's crust constitutes the major
source of terrestrial radiation, which, in most areas, is about 0.3 mSv per year. Amounts of
terrestrial radiation, however, may vary by a factor of 4 to 6 or more in different geographi-
       The remaining background radiation exposure is from man- made sources. Diagnostic
x-ray and nuclear medicineaccount for most of the average estimated annual total of from 0.4
to 1 mSv. Exposure from these sources has doubled in the UnitedStates and many other
countries during the past 20-years. Contributions from nuclear explosions, nuclear power,
and all ather sources account for less than 1 percent of background radiation.
       Most acute or intermittent excessive exposures to ionizing radiation occur in associa-
tion with radiation diagnosis and therapy, nuclear weapon detonations, radiatio device and
nuclear reactor accidents, or improper use of radionuclides. Most of such exposures are to
low-LET x-rays or gamma rays, but direct exposure to nuclear weapon detonations or fallout
or the excessive ingestion, inhalation, or injection of certain radionuclides may result in sig-
nificant exposures to neutrons, and alpha and beta particles, and high-LET gamma radiation.
       ' PATHOGENESIS OF RADIATION INJURY There are many types of cellular
injury following exposure to ionizong radiation. Most important is damage to the genetic
apparatus of the nucleus due to structural alterations of DNA and chromosomes.
       Many types of DNA damage may occur, but most common with low-LET radiation
are single-strand breaks and base alterations. High-LET radiation produces more double-
strand breaks and more complex types of DNA base damage. In both instances, the free
radicals generated by ionizing radiation are largely responsible for the DNA and
chromosomal alterations. The extent to which damaged DNA will be responsible for cell
death or will become a permanent mutation depends on the ability of the cells to repair the
damage. Repair of DNA damage from low-LET radiation is much more efficient than it is
from high-LET radiation. This is extremely important because most of the somatic
mutational and late neoplastic effects in replicating cells probably are due to the persistence
of radiation-induced unrepaired or misrepaired DNA bases.
       Chromosomal damageof many types as a function of unre-paired DNA constitutes the
other major type of radiation-induced injury to the genetic apparatus of the cell. Chromoso-
mal breaks with rearrangements associated with loss of considerable amounts of chromoso-
mal mass usually are responsible for cell death at the first or one of the first few irradiation
mititic divisions. Consequently, the numberof chromosomal aberrations present at any one
time during the postirradiation period will depend on both the number induced and the rate of
cell turnover. Unbalanced chromosomal rearrangements usually disappearrapidly. Balanced
chromosomal rearrangement involving little loss of chromosomal material may persist as sta-
ble intracellular markers of radiation injury for many years. There is strong evidence that
chromosomal rearrangements involving breaks near proto-oncogenes play an important role
in the process of radiation induced malignant transformation.
       Repair of radiation-induced DNA and chromosomal damage is inversely related to the
rate at which the radiation is absorbed. This is particularly true for low-LET radiation, where
a high rate of radiation absorption may increase residual tissue damage by factors of 2 to 10
times that experienced whith a low rate of radiation absorption. Thus a risk reduction factor
of 2 or mor may be applied to the estimation of risk of a biologic effect from exposure to
low-LET radiation delivered at a low doserate in comparison with the risk estimate for the
same effect from similar radiation delivered at a high dose rate.
       Large doses of radiation may produce direct cell death due to membrane or cytoplas-
mic structural damage. This type of interphase cell death of autonomic nervecells, lympho-
cytes, andcapillaries is responsible for most of the early severe clinical manifestations of par-
tial- or whole-body high dose acute relation exposure. Directcell killing from large radiation
doses to localized areas also accounts for the late occurrence of tissue hypoplasia or fibrosis
rather than the development of cancer.
       CLINICAL EFFECTS OF RADIATION EXPOSURE Acute or early clinical effects
are those which occur within the first few minutes and up to about 2 months following
exposure to large amounts of ionizing radiation delivered over a short period of time. They
are due to cell killing, impairment of cell function, inflammation, infection, and hemorrhage.
       ate effects occur after the first few months and up to a few years following exposure.
Late effects are the radiation-related diseases and disorders that develop anytime after the
first few years following previous acute or chronic ionizing radiation exposure.
       Acute radiation effects The early systemic manifestations of acute exposure to exces-
sive amounts of ionizing radiation constitute the acute radiation syndrome. Survivors of the
complete syndrome will experience four classical clinical stages that vary considerably in
time of onset, severity, and duration, depending on the quality, quanlity, and extent of the ra-
diation exposure. The earliest is the prodrome, which consists of anorexia, nausea, and vom-
iting but also may include diarrhea, increased salivation, abdominal cramps, and dehydration.
It commences within minutes to hours of exposure and lasts from a few hours to 1 or 2 days.
This phase usually is followed by a relatively asymptomatic second stage of a few days' to a
few weeks' duration. The third stage usually begins during the second to fifth weeks follow-
ing exposure with the abrupt onset of moderate to severe gastrointestinal tract disturbances
and manifestations of bone marrow depression. The fourth stage involves recovery, which
may take weeks to months.
       Persons who receive whole-body radiation in the range of 50 Cy or more invariably
will die within 24 to 48 h from complications associated with the neurovascular syndrome.
This is characterized by the rapid onset apathy, lethargy, and prost
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