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THE EF7ECTS OF TOTAL BODY X—IRRADIATIDN
IN THE DOG

E.W. Van Stee, 3050, Dove“.
Dept. of Surgery & Medicine
College of Veterinary Medicine
Michigan State University

E. Lansing, Michigan

November, 1960

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ACKNOWLEDGENEHTS

The author wishes to acknowledge the fin-
ancial eunnort for this research by The
Hark L. Morris Animal Foundation and the
Department or Surgery and Medicine, College
of Veterinary Medicine, Hichigan State
University, East Lansing, Michigan. 81n-
oere gratitude is also extended to Dr. U.
V. Hoetoeky, Susan Richards. M.T.. and my
wife, Beverly, for their generous assis-
tance in performing so many of the time.
consuming activities which are necessary
to execute e program such as this.

H mm 3125'?

In the early and mid~1890's two independent obser-
vers were recording the presence of s new stuff or the
universe. A rare and heavy element, uranium, and a com-
bination of an induction coil and highpvscuum tube seemd
to emit mysterious rays, apparently very similar; invis-
ible, odorless, tasteless and insidiously devoid of the
ebility to produce immediate sensation. Such was the
humble beginning, little more than a half—century ago
of a number of branches or modern science which collec.
tively include at least some aspects of most present-day
scientific endeavor. Today 'x-rsy' and 'radioactive' are
household words. Today man has progressed from discharg.
ing en= electroscope in the presence or s radionuclide
to e high degree of mastery over the integration and dis-
integration of the atom. Even the dream of the ancient
alchemist is reality. Transmutation or elements is every.
day practice in atomic research installations throughout
the world (1). I know of none, however, which are per-
tioularly interested in spending the thousands of dollars
required to produce a few grams of gold from some base
metal. Han, instead, stands in awe of bombs created
with.his own hands; not mere toys of dynamite sticks
or measured in pounds or even hundreds of pounds, but

rather, compared to thousands or millions of tons of TNT.

-1-

These bombs unharness massive quantities of mechanical
and thermal energy. Also they yield those same radi-
ations that led to the discharge of the electroscope

but in such massive quantities and of such energies that
they may annihilate cities of men without leaving one
mark on one body.

In 1901 Professor w. G. Roentgen (2) of Wdrtzburg,
Germany was awarded the Rumford medal of the Royal So-
ciety of London and the Nobel prize for physics for his
epoohpnaking discovery of x-rsys which now bear his name,
'roentgsn-rsys'. In 1903 Pierre and Marie Curie were
awarded the Davy medal by the Royal Society for their
work on the preperties of radium (3). In the same year,
Jointly with Henri Booquerol, they were awarded the
Nobel prize for physics. M. Becquerel in 1896 had dis-
covered thet uranium spontaneously emitted rays similar
to those described by Roentgen. New known as gamma-rays,
these also have been known as 'Becquereloraysd. Ruther»
ford designated the various rays emitted from radioactive
substances as slphs-, bets—, and gamma-rays according to
their behavior in a magnetic field.

Roentgenersys are part of the continuous electro-
magnetic spectrum (1) which includes the longest radio
waves with wavelengths of hundreds of meters to the

.2;

hardest gamma rays with wavelengths of less than 10'“

Angstrom.units.

At the very inception of Roentgen's work with his
newly discovered rays possibilities for their apelication
to medicine were observed. One of Roentgen's first obser-
vations was that when he passed his hand between the
radiation source and a barium-platinoacyanide plate a
shadow image was cast upon that fluorescent screen of
the structures of his hand according to their relative
densities. He saw the bones of his hand while his hand
was apparently completely intact. Such.was the first
flucrscopic image. Since that time we have learned
that not only may we record radiographio images of deep
body structures upon s photographic plate and observe
them in motion upon a flucmroopic screen but also we may
direct the rays toward specific diseased tissues and
electively destroy them with a minimum of damage to surb
rounding tissues. This Opens the broad field of radiation
therapy and medicine. Since sprays are capable of des—
troying tissues they become integrally involved in the
field of radiation biology which deals with.the effects
of ionizing radiations upon the living organism.

The recent threat. and terrible realization by the
Japanese, of atomic war has spurred research in the field
of atomic medicine. The effects, immediate and long
range, of single or multiple exposures to ionizing radi-

ttic
59‘.)
or 1'

ON
Use A

.— J
‘D
c—O‘
L‘-

etions are being studied. These may originate with the
detonation of a.bomb of fissionable material, a cobalt

or radium ‘bomb' used in radiation therapy or the common
office xaray'maohine. They may be directed toward iso-
lated areas of the body or permeate the entire body. In
our vast knowledge of so many aspects of radiation bio-
logy we are cognizant of the fact that there is yet much
to be learned. Strontium—90 originating from fallout
from test nuclear explosions may be consumed by dairy
cattle, secreted in the milk, consumed by children and
subsequently be reaponsible for an apparent increase

in the incidence of leukemia. These are the speculations
which make it imperative that we move forward with as much
haste as is consistent with accurate study and experi-
mentation.

(zgytfifi) Living organisms may be composed of one cell or
billions of cells. Since the basic effect upon the liVb
ing organism of penetrating radiations is on the subcel.
lular level (u) all organisms are similar in many respects
in their responses to irradiation. A colony of unicellular
organisms growing on an agar plate may be completely
inactivated or a highly complex mammalian organism may be
killed by large quantities of radiation (5). A common
designation of an amount of radiation to which an organ-
ism may be exposed which is a function of the organism
type itself is the LD5O. The LD50 when applied to radiation

-zs;

dosage may be defined as that amount of radiation neces-
sary to kill or inactivate fifty percent or a given pop-
ulation (or more literally. the I'lethal dose-50').

Other quantifications of radioactivity (6) have been
formulated according to necessity. A curie is equiva.
lent tc 37 x 1012 nuclear disintegrations per second.
”Dose” refers to energy transferred to unit mass of
irradiated object. Related to rurcly physical units

one 'rad“ is equivalent to 100 ergo per gram or 66 elec-
tron volts per cubic micron if the density of the object
is assumed to be 1.05. One roentgen is usually equivalent
to 0.93 rad. Other units such as “roentgen equivalent
man“ or FEM are in use in some areas.

When sprays, and subsequently ionizing radiations
from other sources, Vere first employed in the selective
destruction of neoclastic tissue it was noticed that a
peculiar syndrome often followed irradiation of the sub—
ject which varied from mild symptomctology to death.
These symptoms generally included weakness, anorexia,
vertigo, nausea and emesis. More severely affected
individuals would show diarrhea and dehydration accom.
panied by generalliaed hemorrhage of varying degrees.
Another important effect was upon the very sensitive
hematOpoietic system which led to a marked reduction
or a complete cessation of the formation of the cellular

elements of the blood. This general syndrome has been

variously designated “radiation sickness“ or ''radiation
poisoning'(7~13). It was later discovered that these
symptoms could be reduced in severity or alleviated
entirely by dividing doses and spreading them over a
longer period or time. An indiVidual's tolerance seemed
to be a function of not only the quantity and quality

of the radiation but also the period of time over which
it wee administered. Even at very high dosages the effect
of irradiation is not immediate. There is a latent period
which may vary from minutes, to perhaps, years in the
case of genetic damage. Following the latent period
there is what may be termed a prodromel stage (11) in
which the individual experiences the first signs of
radiation sickness. This usually begins with a vague
uneasiness and progresses to gastrointestinal distress.

An initial loss of appetite pragresses to front emesis.
Continued vomition leads to dehydration and the ensuing
gastrointestinal hemorrhage may terminate in death at
this point. If the individual survives this gastrointes-
tinal obese the eriects of hematopoietie depression (7,16)
begin to shoesr. There is e progressive enemia and
leukopenia which may be observed by clinical examination.
The general anemic debility is grossly manifested by
shortness of breath. increased heart actiVity and loss

or weight. When the leukOpenia and hence defense mach.
unions or the body have been depressed to the point that
they no longer are able to reliet the constant challenge

;6;

by invading organisms which characterizes the complex
ecological eyetem in which everyone and everything lives.
oeoortuniet bacteria and other microorganisms may enter
the general system. They may establish more or less
tyoical although severe infectious disease syndromes.
Feeulting septicemia or toxemia may then lead to death.
Death due to ionizing refiietion may take the form
of a syndrome different from that previously described.
That is the clinical picture presented folloving excee-
eively high doses of total body radiation. The symptoms
manifested are those of central nervoue system involve.
ment (8, 9, 17) anfl usually occur so soon following
irradiation that few signs of the gastrointestinal phase
are evident. Emeeie, when present, is probably due to
central stimulation. Monkeys irradiated too to h0,000 r.
(roentgen units) on the higher end of the doeage range
uniformly showed very early (at very high levels while
still in the relinticn field) signs of uneasiness fol-
lowed closely by convulsizns ani coma. Convaleive gesoing
motions were frequently cbserv a to persist for one or
two hours folloving remivel from the radiation chamber.

The source of relieticn (gnome) in this series was cobalt-60.

( 0

Since aenth eneuéd in such a ehcrt tine {on th. order of
a few minutes or houri) gross lesione were few and not

particularly significant. KioroscOpic lesions were like-
wise generally insignificant everywhere but in the brain.

Hnymalzer 5.; 5;. (15) and Vogel :1 3;. (19) have given

-7;

excellent detailed descriptions of the central nervous
system histopatholog1oal changes in similar exn5r1mente.
Fiva basic 1551cn5 were obgervod: (a) oyknoels or the
cerebellar granule 06119, (b) nyknnq15 of pituitary baso.
phlls, (a) cerebral vasculltie, (a) fooal meningitis,
and (e) ohoroii pleaitle. V113 microioooio abnormalities
of the g~'trnlntent1na1. tr:ct were oheervea. Bong marrow
15 aonnrently about the wont 55n51t1ve tinque of tha

fly anfl C5grntr'tive changes may be ohgervcfi 1n monkeys
as early as 3% hours postirreflirtiwn.

re 53 scnstr:.tpfi in tho NonLey, three distinct
syndromes (9) may occur following 1rr9diatlon aspeniing
unon the doSuge. Four hunéred to 830 r. led to hemato~
ooietio death, 030 to 7500 r. 155 to the gastrointestinal
gyndrome and over 90C0 r. produced the central nervous
system death.
In anotr er aer15 s of experiments (10) groups or

Rheaus mlznkeya wer= sub oted to high level raniatlon
for the purpose of obs+rv1ng tha prompt 5ff5ct5 upon
th5 acid-b556 talancs, uric acid, glucose and rrfie amino
aotfla cf the blood. The trend indicated that the animals
in the? 1vhor do5zg5 rangaa (5000 to 30,300 r.) tended
to have a lower blood pH. A corroevond:zg 150310 Hold
increase par allolod the pH dro;. Ry compari5on with
602 tensions 1t 5'53 Sh'swn that the matabolio aoidosls

was greater than the respiratory alkalosls (due to

.:.8.

increased respiratory rate). Study of two— imensional

p.

ohromatograma revealed that plasma glucose decr5555
and plasma brie acid increased; A two-f 01d 1m: m‘ 525
in free amino acids at the 5000 r. Ifivel 559 observed.
This did not, hovfivrr, increase with in5555355 donxge.
In mice, vats and dog; "'rtmoifit-«ti
produced by doses of total body x-ifi=5ۤ~tlfin 1f the order
of magnitude of 1°00 f? 10,306 r. (1?). fi~ath ttualiy‘
occurs abCJt SPree to fi.ve ’5y5 .o5tlrrndistion. 3"“b
vival time does act 955m to V?17 much cith the dosages
Within this range notil *h“ u we? limit 1: approached.
Here central nfirvova system symptoms 55555:. In :;ra.ther
zariee conducted by t};e UL AF (9) gr::up5 of Rhesus monkeys
were subjected to 1.5 to 7.5 kiloroentgens (kt) from
32 cobalt-60 sources located in a spherical arrangegont
around a oeosule containing them individvally. Poath
occurred in four to nine days with severe gastrointestinal
eymotm as. Postmortem histop5tholcgioal oxaminaticn
revealed congestion, ulczraticn and various gradetions
of mucosal atrophy throughout the GI tract. Eyt c eive
Interstitial renal hemcrrhsge 555 ob¢erved with the pre-
sauce of numerous fool of bnotaria throughout the paren-
ohyua. It is euggoztad that bacteria may filay an imfiort-
ant role in the development of intestinnl ulceration

following suwralsthal doves of ionizing radiation.

~94

Anong the many studies which have been conducted
by the USAF School of Aviation Medicine is one which
described the changes in the peripheral blood picture
of the Rhesus monkey due to highpenergy ionizing radiation
(7). The source of the radiation in this case was a
test atomic explosion. The animals were adequately pro-
tected from blast and thermal damage but allowed to be
exposed to nearly the full gamma shower from the explo-
sion. Deaths among the irradiated individuals occurred
at 16 through 22 days with the exception of three (15%)
of the subjects which appeared to be in good health
three months later. The estimated dosage received by the
various grouse was from “10 rods to 520 rads. The mean
values over a thirty day period (most individuals died
along the way) for RBG'c. hematocrit and hemoglobin
decreased to around 50% of the control values for each
group. Over the same period platelets decreased at 15
days to less than 10% or the control values but than rose
to 301 or more by the time death occurred (with the ox-
ception of the highest dosage group which died at the
time of the lowest mean percent value). The total leak.
ocytc picture 0103011 paralleled the platelet change
with the highest dosage group (520 radc) dying at a time
when the peripheral circulation was practically devoid
of white cells. The others survived past this time to

regenerate as much as 65% of the control level of WBC's.

i-l C .-

. 5-.

F EGG? EAL-1K; 3, g

A study conducted by the Research Laboratory of the

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Department of Surgery and Medicine, College of Veterinary

Medicine, Michigan State University dealt with the changes
in the peripheral blood picture of the dog due to supra.
lethal doses of ionizing total-body radiation.

The source of radiation used was the Maximar 250-111
x~ray therapy machine manufactured by the General Electric
Corporation. The mean output was determined to be 57r./hin.
by means of a Victoreen remeter.

Dogs were obtained from an eXperinental beagle
colony and a pound. For the higher dosage levels pure-
bred beagle bitches over two years old were employed.

For the lowest level medium-sized mongrel bitches were
used. All dogs had received modified live virus infec-
tious canine distemper vaccine at least two weeks prior
to initial blood sampling. The two mongrels were splen-
ectcmized during a previous study in which they had been
used. They were maintained in individual stainless steel
kennels and fed once per day. The diet consisted of
Froum's meal (Fromm Laboratories, Grafton, Wisconsin)

and water mixed with a small amount of canned Hill‘s
ration (Hill Packing 00., Topeka, Kansas) as a condiment.

A number of routine blood and narrow determinations
were performed as a check procedure on the effect or the
radiation on the hematOpcietic system. Thirty years ago
it was determined that x—rays woufd produce aplasia of

the bone marrow (21) and hence a progressive blood cyto-

~11-

penis. Serum was simultaneously obtained for analysis
by paper electrOphoresie.

Blood hemoglobin was determined by the method of
Evelyn and Halley (20) using the cyanmethemoglcbin res.
gent. Hicrohematocrits were performed with heparinized
capillary tubes and the International hicrocapillary
Centrifuge. White blood cell counts were performed
using runk'e reagent and Yankee certified diluting pi-
pettes. The blood and marrow smears were stained with
Wright's stain for the differential white blood cell counts.
Bone marrow samples were obtained by eternal puncture.
The area over the nth or 5th sternebra was infiltrated
with 0.5% lidocaine (Xylccaine, Astra) and puncture ef-
fected with.three inch, 14 gauge needles. Marrow sub-
stance was withdrawn into five cubic centimeter syringes
and smeared immediately.

Serum samples for electrophoretic analysis were
obtained from blood withdrawn by Jugular or cephalic
venipuncture. Ten cubic centimeter blood samples were
allowed tc_clct for at least two hours or until serum
appeared to be supernatent and the clot began to retract
from the sides of the tube. They were then subjected to
several minutes of centrifugation at 2000 rpm. The serum
was decanted and transferred to cork steppered glass
vials. Because it was not always convenient to apply
the samples to the electrophoretic cells on the same day

as they were obtained it was necessary that they be

-12;

frozen and held until a convenient time. To minimize
variation due to freezing and storage all samples were
frozen before use and held for at least 2h hours at

.200 Centigrade. Sampling was performed between two and
four o'clock PM to minimize possible diurnal variation.
Since the animals were fed daily between five and six
o'clock FM variations due to recent ingestion of a meal
were also negated.

The basic equipment for electrOphoretic analysis
consisted of the Model H Paper Electrophoresis System
manufactured by the Beckman Instrument Company, Spinco
Division. The paper electrophoretograms were stained
according to procedure B described in the accompanying
manual using brom phenol blue. The strips were then
subjected to analysis on the Model RB Analytrol, a re-
cording densitometer-integrator. Resulting curves were
then analyzed by hand and relative percentages of al-
bumin, alpha1-, alphazu, betal, betazu and gamma-globulin
and the albumin-globulin (A/G) ratios were determined.

Each individual served as his own control. Base
lines were established for each determination on each dog.
Three values were obtained before irradiation at intervals
of several days. Six hours following irradiation and
every twenty-four hours thereafter blood samples were
withdrawn for analysis. In the two higher dosage groups

sampling was continued to the day of expiration, sampling

-13.

in the moribund state when possible. In the lowest

dosage group sampling was continued at twenty-four hour

intervals through the fourteenth day at which time impending

recovery was apparent.
{1E¥;;LT"3 The following results have been tabulated giving
the individual values and the arithmetic means for
the two subjects in each group (Tables I - X). The
corresponding plots are of the mean values only
(Figures 1 - lo). Table XI illustrates the depression
of the hematopcietio system by means of differential
cell counts.

Following irradiation a latent period of 18 to
2b hours was observed during which no effects attri-
butable to the radiation were observed. After the
first day, however, the animals in all three groups
seemed to be somewhat depressed. One of our group
rather picturesquely described their appearance as
“gray“. Their heads drooped slightly and they appeared
not to be as bright as they had previously. After
#8 hours all deve10ped diarrhea which, in the ease
of the two higher dosage groups, progressed to diar-
rhea accompanied by melons vera. At 96 hours the
higher dosage groups were prostrate and in complete
check which rapidly progressed to coma and terminated
in death after four days in the 750 r. group and five
days in the 1000 r. group. In the moribund state each

individual developed the coldness and insensitivity

-1h;

of the extremities and final complete anesthesia
typical of the shock syndrome.

The lowest dosage group (500 r.) developed a
transient general depression which.correspcnded to
that of the higher dosage groups. However. they failed
to develop a severe diarrhea indicative of the gastro-
intestinal syndrome. They recovered from the initial
depression but did not return immediately to their
former condition. This was related to the accompanying
anemia. When regeneration of bone marrow began and a
subsequent increase in the number of circulating cel-
lular elements of the blood occurred there was a no-
ticeable increase in alertness and activity. From the .
white blood cell counts (Table x and Figure 10) in was
estimated that this turning point developed during
the 12th through lath postirradiaticn days.

The general response of the dogs corresponded
closely to the response observed in Rhesus monkeys
by Leftingwell (7) during the early part or this year.
The monkeys had been eXpoeed to radiation (genus)
originating at an atomic eXplosion. The dogs in the
higher dosage groups died at a time when the peripheral
circulation was practically devoid of white cells.
There was little difference in the responses of the
two groups at 750 r. and 1000 r. The 500 r. dosage
group, however. differed considerably in failing to

-15.

develop the symptoms of the gastrointestinal syndrome
and eventually beginning regeneration of the formed
elements of the blood. From this small sampling it
is supposed that the LDSO for total body irradiation
of the dog lies somewhere between 500 r. and 750 r.
At 500 r. there was a transient debility followed by
recovery. At 750 r. and above the gastrointestinal
syndrome developed and the dogs passed throughfthe
series of symptoms. became comatose without respect
for the magnitude of the does. It is expected that
at much higher dosages the central nervous system death
would occur as it does in monkeys.

Examination of Table I and Figure 1 reveals the
steady decline in the level of albumin detectable by
paper electrophoresis. This is consistent throughout.
all three groups. In the 500 r. group the decline was
terminated by the 9th or 10th day and began to rise.
This change preceded the rise in white blood cells
(Table x and Figure 10) by about #8 hours.

In Table II and Figure 2 it will be seen that
there is only a very slight decline in the levels of
a1pha1-globulin. This small change would not be ex-
pected to be of physiological significance.

It will be seen by examination of Table III and
Figure 3 that there is a significant rise in the alphaz-
globulin in all three groups which terminates in death

~16-

in the two higher dosage groups but which is resolved
back to the original levels in the 500 r. group by
the time cellular elements and albumin have begun to
regenerate.

A different pattern of deveIOpment may be observed
in Table IV and Figure #. The betel-globulin at the
lethal levels (750 r.. 1000 r.) rose steadily until
death. it the 500 r. level the beta1-globulin remained
essentially constant.

The relationship between the betal- and betaz-
globulins becomes apparent when comparison is made
of Table IV and Figure h with Table V and Figure 5.
The response of the beta2-globulin is the inverse of
that of the betalaglobulin. At the lethal levels
the globulins drOp and at the 500 r. level they again
remain constant. This would indicate that radiation
has the effect of causing the shifting of part of
the betaz component to the betel component of lower
electrophoretio mobility.

Examination of Table VI and Figure 6 indicates
that the gamma.globulin response is similar to the
betalnglcbulin response. it the lethal levels there
is a rise and at the 500 r. level there is no signi-
ficant change.

Thecnet change in the sum of the globulin con»
ponente is not particulary significant. This is re—

-17.

flsoted in the albumin-globulin (Alb) ratios (Table VII
and Figure 7) which closely parallel the albumin change
(Table I and Figure 1). In the case of the lethal
levels there is a sharp decline in the A/G ratios
which is terminated in death. In the case or the
500 r. level there is a decline and subsequent recovery
which corresponds to the recovery or the albumin levEle.
Table VIII and Figure 8 represent a complex change.
The effect of radiation upon the hematopoietio system
led to a reduction in cellular constituents and heme-
globin or the blood. The result of the gastrointes-
tinal syndrome was rapid dehydration and subsequent
hemoconcentration. At the 500 r. level there were
no signs or diarrhea and the animals' fluid balance
remained essentially normal. The hematOpoietic depres.
sion led to a reduction in the number of circulating
erythrocytes and, hence, hemoglobin. In the two higher
dosage groups the gastrointestinal syndrome terminated
in death. The onset of the hematopcietic depression
was more rapid than the homeconeentration as may be
determined by examining the initial 310999 of the
curves. As the hemorrhagic diarrhea became more as.
vere and the blood became more concentrated henocon.
centraticn compensated for the anemia by the 3rd and
hth days. By the 4th.and 5th days a combination of
hemoconcsntration due to the severe intestinal hemorb

rhage and diarrhea plus the hemoconcentrating effects

~18-

of shock became so marked that the hemoglobin per
unit volume scared to very high levels. This was
especially evident as the blood samples were drawn.
The subjects were, by this time, in a comatose state
and the blood wee so thick that it was very difficult
to draw into a syringe through n 20 gauge needle.

The striking eimilnrity or the microhematocrit
curve. (Table IX and Figure 9) and the hemoglobin
curves (Table VIII and Figure 8) indicates that in-
diVidual cells had not changed in hemoglobin content.
The resistion-induced bone marrow aplgeiehad caused
a complete cessation of cell production and subsequent

changes in erythrocyte and hemoglobin values were due
to a changing environment surrounding those cells which
were already present in the peripheral circulation.

Table I and Figure 10 represent the change in
white blood cells due to the bone marrow apleeie.

At the lowest dosage the curve is very similar to

the curve representing the change in packed cell vol-
ume (microhemetocrit). Since the life of the circulating
thitfi blood cell is much shorter than that or the red
blood cell cessation of their production rapidly leads
to a severe leukoPenin deepite the effects of hemo-
concentration. This is evident when it is observed
that the curves for the higher dosage levels decline
as least as rapidly as the low dosage group. In the
case or severe depression of body defense mechanisms
following irradiation the lives of the circulating
white blood cells (largely phngccytic granulccytee)

are shortened even more as they are called to micro-
organic invasion sites to strengthen weakened defenses.
This phenomenon illustrates one of the most unfavorable
results of exposure to ionizing radiation at sublethal
dosage levels. The body's first line of defense, the
white blood celle, may be functionally impaired or
eliminated entirely. This leaves the body open to
invasion by bacteria and other microorganisms which
may , in a marge part, be responsible for some of the
most serious effects of radiation sickness.
Table XI shows the distribution of cells in the

hematopoietic tissue itself (bone marrow). Dogs 1

and 2 were at the 500 r. level, dogs 3 and h were

at the 750 r. level, and dog 6 was at the 1000 r.
level. In comparing the base line values with those
following irradiation it may be seen that there was

a disappearance of meat juvenile forms leaving only
surviving mature white anti band cells which had been
produced before the bone marrow became aplaetic. It
was observed while making the differential counts that
there were present numerous unidentifiable cytoplasmic
masses probably representing degenerating white cells
or white cell precursors. Because these could not be
classified they were omitted from the differential
cell count determinations of marrow samples taken on
postirradiation days. These degenerating forms were

not present in the pro-irradiation, base line samples.

-20-

r ..
{{J’ ‘\ {V} 3".) f". if. ”I
.V '

A.study was undertaken by the hichigan State
University Department of Surgery and Medicine. The
purpose was to determine the effects of lethal doses
of roentgen rays on the blood cells and serun.proteins
of the dog. The three groups of two dogs each were
subjected to graduated totalabody doses calculated
so that the lowest dose would be slightly in excess
of the total-body 1.1350 for humans (#50 in). Unexpect-
edly. the lowest dosage group survived. This response
provided data for a comparison between lethal and sub.
lethal doses in addition to absolute blood effects.
Routine blood counts and periodic hone narrow differ-
ential cell counts were performed as a check of the
efficacy of irradiation. Simultaneously serum protein
distributions were determined by means of the Spinco
Paper Electrophoresis System. It was found that irra-
diation in all three groups produced aplasia of the
bone narrow. The decline in number of circulating
white blood cells was not so severe in the low dosage
group which survived as it was in the two higher dosage
groups which succombed. Initially the hemoglobin and
packed cell volumes (microhematoorits) decreased in
response to the cessation of cell production. These
effects were soon negated, however. by the combined
effects of severe hemorrhagic diarrhea and shock

which led to a state of hemoccncentration and subse-

-21..

quent sharp rise in both hemoglobin and nicrohematoorit
values. This rise was terminated by the death of
the subjects.

Because of the small number of individuals con-
sidered in the study it was difficult to evaluate
the synptomatclogy of radiation sickness in the dog
versus quantity of radiation to which it is exposed.
Based upon the number of dogs used it would appear
that there is little relationship between these two
factors beyond the demarcation between threshold doses
required to produce a particular syndrome. The range
of dosage levels producing the gastrointestinal syndrome
may be rather large. But within that range there
is probably little difference between the effects of

a high dose and a low dose.

«22-

 

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43-

FLARE I: The radiation source or the Mazimar 2500111

xaray therapy machine is located within a concrete

and tile, lead-lined room and Operated through a panel
in an adjacent room. A View or the therapy room from

the control panel is secured through a two-inch thick

lead olate glass window.

PLATE II: The Model RB Analytrol is a recording den-
sitometerbintegrator which is used to analyze c1ectro~
phoretcgrans.

PLATE III. Durrum type electronhoretic cells are shown
loaded with the filter paper strips which serveoas

a support and transport medium for the separation

or the protein constituents of serum in a veronal
buffer system.

PLATE IV: Stained electrophoretcgrame are shown with
those fractions of highest mobility toward the bottom.
The most rapid and darkest bands at the lower extremes
of the stained areas represent albumin.

-3h.

 

 

 

 

 

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PLATE V: All dogs were maintained in separate stainless
steel kennels.

PLATE VI: Blood sampling was accomplished by Jugular
Venipunoture. when this was difficult the cephalic
vain was used.

FLATS VII: Bone marrow sampling was effected by punc-
ture of the medullary cavity of the nth or 5th sternebra
with a lb gauge needle. The only anesthesia necessary
was local infiltration of the shin.

PLATE VIII: At the lethal dose levels dogs died in
a comatose state following a severe bloody diarrhea.

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. 334

   
   

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(2)

(3)

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(5)

(6)

(7)

(8)

BIBLIOGRAPHY

Brey Wallaces . Jr. We mflzgiggl
' . New lent: Appleton. en rofte.

no. 9 . p 10h

Roentgen, w. G. e cfifn, . Bitsungber. warts-
burs er Physik~He e. J . l 65 as reprinted
in mien der Phyeik and e (None Folge).

Vol. 64. p1. 1898 as reprinted in the Smithsonian
Treasury of Science. True, Webster P., Ed. New
York: Simon and Sohuster, Inc. 1960. Vol. I.

pp 166-190

Curie, Pierre. 3;, . Revue Scientifique. Feb.
13, 190: as rcprinte in the Smithsonian Treasury
of Science. True, Webster P., Ed. New‘York:
Simon and Schucter. Inc. 1960. Vol. I. pp 253-

277

Wood, 2. H. Bone Aegegtg gellglgg £33122l2%3819
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Inc. April. 1959. pp 282-288

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Ellie J. P. Jr.‘_1_a . £29321 Er e figkghp
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0. 7. Department of Physiology and Biophysics
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tion medicine, USAF.Aeroepacc Medical Center
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anaeeange. A. and Gricourofr. G. translated by
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liglngg. 2nd Ed.i9new Ices an London: Grune

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