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November 1968
FISSION PRODUCT
INHALATION PROGRAM
ANNUAL_ REPORT
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1967-
..~ ...... by the
Staff of the
Fission Product Inhalation Program
::-LOVELACE.:FOUN,_D_ATION: -for MedicalEducatlon and Research 520o Gibson Boulevard, SE
Albuquerque, NeW Mexico 87108
Prepared for the U.S. Atomic Energy Commission, D!vision-bf:Bio!ogy and Medicine, under Contract AT(29-2) 1013.
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LEGAL NOTICE
This report was prepared as an account of Government sponsored work.
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As used in the above,
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INTRODUCTION
The prime objective of the U. S. Atomic Energy Commission-Lovelace Foundation Fission Product Inhalation Program is to develop knowledge that will contribute to an improved understand- ing of the biological consequences of inhaling radionuclides, such as might be released in the event of nuclear accidents. The ultimate goal is to establish the relationship between the radiation dose pattern resulting from various levels and types of exposures and the resulting biological response. The major stimulus for development and continuation of the program stems from uses of nuclear energy such as nuclear power reactors, space nuclear systems, and nuclear propulsion systems that may result in potential accident situations with dispersion of radioactive aerosols. Becausethe study of itsof (^) 90Sr-90y,importance, 91y,special 95Zr_95Nb attention has been devoted to the power reactor situation through ’ 106Ru_106Rh^ ’ 1311,^ 137Cs^ 137tuBa^ ’ 140Ba-140La,^ and
144Ce-144pr, radionuclides that predominate in a reactor inventory after a period of sustained operation. Recognizing the increased use of plutonium and transplutonium radionuclides and their potential abundance in breeder reactor systems, their toxicity has also become of interest to this laboratory. Studies are being conducted to evaluate the importance of the many factors influencing the toxicityof inhaled radionuclides. These include: (i) the radiologic characteristics of radionuclides such as half-life and emission (alpha, beta, and gamma} whose differences result in a spectrum of radiation dose patterns, (2) particle size and solubility, (3) the physical and chemical character- istics of aerosols, and (4) physiological characteristics of the animals, all of which are important in determining the ultimate toxicity of a radioactive aerosol. The prime experimental subject in the program, the Beagle dog, has been used for several reasons including: (I) its moderately long lifespan, which may be of importance in extrapolating findings to man; (2)its size, which allows each animal to be studied intensively as a clinical subject much as a human patient; and(3) the desire to make use of the wealth of information being obtained in other long-term radiation toxicity programs using the Beagle dog, and to develop information that will complement the findings of other programs. Additionally, more limited studies have been conducted with Chinese hamsters, mice, rats and guinea pigs to complement the Beagle dog studies. Such studies are frequently desirable be- cause of some unique characteristics of a particular species; such as the chromosome pattern of the Chinese hamster, and because data obtained on multiple species may be used to advantage in the extrapolation of information to man. Two major characteristics of the program that are essential to its success are a strong multi-disciplinary team orientation and an overall radiation dose-response orientation. The extent to which both these characteristics are put into effect in the program is especially evident in the papers in SectionI of this report. The first three papers describe continuing efforts to evaluate the (^) toxicity of inhaled 90SRC12, 144CEC13 and 91yc13 in the Beagle dog, studies initiated in pre- viousyears. The next two papers, on the toxicity in the Beagle dog of injected 137CsCland inhaled 144Ce in fused clay, describe long-term studies initiated during the past year. The last three
papers in Section I relate to studies being conducted in rats and Chinese hamsters. A team effort is involved inall of these studies with observations being made in the areas of whole-body counting; radioanalysis of aerosols, excreta, and tissues; clinical examinations; radiography; biochemistry;
been awarded Master of Science degrees based in part on their thesis research performed here; a third individual, Barbara Nylund Morgan, will complete her thesis in the near future. A fourth graduate student, W. W. Pillow, supported by a U. S. Public Health Service training grant from his home institution, the University of Arkansas, initiated his thesis research here in the summer of 1968. His major professor, Dr. C. E. Breckinridge, spent a portion of the summer here as an AWU Faculty Participant. During the summer of 1968, one individual participating in the Univer- sity of New Mexico RadiobiologyInstitute spent her summer on a research project in this labora- tory. In addition to the above, 10 students; undergraduate, graduate, medical or veterinary medi- cal were employed on a temporary basis during the summer of 1968. In addition, where it has proved mutually advantageous, students were employed throughout the year on a temporary basis. It is noteworthy that one of these, Dr. J. Levy, utilized research performed under the Fission Product Inhalation Program as a thesis for his Ph.D. from the University of New Mexico. Hope- fully, similar efforts can be continued and perhaps broadened in the future, since the presence of students serves as a stimulus to the permanent participants in the program and further, the unique and extensive research program being conducted provides innumerable opportunities to contribute to the education of students.
iii
FISSION PRODUCTINHALATION LABORATORY
An aerial view of the Fission Product Inhalation Laboratory Facility located 10 miles
south of Albuquerque, New Mexico on Sandia Base. The facility operated by the
Lovelace Foundation for Medical Education and Research for the Division of Biology
and Medicine, U. S. Atomic Energy Commission was constructed in several incre-
ments starting in June 1962. The facility now consists of (1) a central laboratory
and office building which includes a specially designed and equipped inhalation expo-
sure complex, (2) a veterinary hospital, (3) a canine metabolism building with space
for housing Z00 dogs, and (4) eight kennel buildings each capable of housing 100 dogs.
Currently a ninth kennel building is under construction, and architectural and engi-
neering work is being done prior to construction of a small animal holding facility.
Additional facilities located at the Lovelace Foundationheadquarters site in southeast
Albuquerque are also used in the conduct of the Fission Product Inhalation Program.
iv
TABLE OF CONTENTS (Cont’d)
Pulmonary Lavage - A Technique for Use in Dogs and its Clinical Effects ...................................................................... (^191) Lipid Composition of Surfactant and Lung Cells of Beagle Dogs ...................... (^196) Lipid Analysis of Tissues from the Beagle Dog .................................... (^202) Pulmonary Lavage as a Therapeutic Measure for Removing Inhaled 95Zr-95Nb Oxide from the Lung ................................................ (^207) Effect of Age~ Strain, and Whole-Body X-Irradiation on Transplantability of90 Sr-lnduced Chloroleukemia in Rats .................... ..................... (^217) The Effects of Inhalation of 90SRC12 on the Excretion of Urinary 17-Ketogenic Steroids in Beagle Dogs ....................... , ................................ (^) 22Z Evaluation of Hypothyroidism in a Beagle Dog Colony .............................. (^) 225 Beagle Dog Production Experience at the Fission Product Inhalation Program - 1961 through 1967 ................................................... (^) Z An Improved Dog Breeding Program ............................................ 236 Appendix ........................................................................... (^241)
A,
B. C. D.
E,
Status of Longevity and Sacrifice Experiments in Beagle Dogs ....................... (^) 24l Publication of Technical Reports ................................................. 254 Publications in the Open Literature ................ ......... (^). .................... 255 Presentations Before Regional and National Scientific Meetings and Educational and Scientific Seminars ............................................. 258 Staff Roster ................................................................... 260
SECTION I
DOSE- EFFECT STUDIES
TOXICITY OF INHALED 90SRC12 IN BEAGLE DOGS. II
ABSTRACT
Studies on the metabolism,dosimetry, and effects of inhaled 90SRCI
in the Beagledogare continuing in an effort to provide a basis for
assessingthe consequencesof inhaling 90STsuchas mightbe releasedin
certain nuclear accidents. Seventy-two dogs have beenexposedto
aerosolscontaining90ST,resulting in initial bodyburdensrangingfrom
2.6 to 280 #Ci 90Sr/kg. Forty-eight of these dogsare being maintained
for lifetime observationandhavebeenplacedin a longevity study con-
sisting of four groupsbasedon their retained 90STburdenat 14 days
postJnhalation. Groupmeanswere 1.4, 6.2, 30 and 75 #Ci 90Sr/k#.
Twenty-four dogs with a 14-day retained 90STburden of 31 #Ci/kg
havebeenassignedto a sacrifice study. To date, eleven dogshavedied
or wereeurhanized;six during the first 31 daysafter inhalation with
severe hematologicdyscrasia, one at 585 days with leukemia, one at
1099days with an osteochondrosarcomaand three at about 1000days
after 90STinhalation with angiosarcoma.Serial observationsare con-
tinuing on all surviving dogs.
INTRODUCTION
90Sr* is one of the fission product radionuclides that predominates in a nuclear reactor in-
ventory after a period of sustained operation. For this reason and because of its high probability
for release in certain type of reactor accidents, as well as its long half-life and energetic beta
emissions, it was one of the radionuclides selected for intensive study in this program.
The experimental design incorporates two groups of dogs: (1) alongevity study consisting
graded exposure levels in which dogs are being maintained for lifespan observation, and (2) a sac-
rifice study in which dogs are being serially sacrificed to provide specimens for histopathologic
and other studies.
To simulate the type exposure that would most likely result from an accident, the dogs were
given a single inhalation exposure. For the longevity study, a total of 48 dogs have been exposed
and are being maintained along with 15 control dogs. When ranked according to initial body burden
of 90Sr and divided into four groups of 12 each, the average 90St body burden for dogs in each of
the groups was 4.1, 23, 100 and 230 uCi/kg. Differences are observed among individual dogs in
the amount of initially deposited 90Sr that is excreted in the first few days post-inhalation, such
that the ranking of dogs by 90St burden in uCi/kg changes from the day of inhalation exposure to
14 days post-inhalation. At the latter time, the four group averages were 1.4, 6.2, 30 and 75HCi
90Sr/kg. A parallel sacrifice study, which consisted originally of 24 exposed and 10 control dogs,
is still being maintained. The average initial body concentration of 90St was 88 ~Ci/kg and the
corresponding 14 day post-inhalation value was 29 ~Ci/kg. (See Appendix A for additional infor-
mation on individual dogs. )
*90Sr as used in this text refers to 90St in equilibrium with its daughter, 90y.
Table I Parameters of Multi-Component Exponential Retention Equations With 2, 3, or 4 Compor~ent Fits for 90Sr Longevity Dogs*
Parameters
Number of Components Used to Fit Retention Curve
2 Components (^3) Components
ai (fraction) .58 (+-.^ 03)^ .64^ (-+. 08)
×l (day-i) 1.4^ (+-.3)^ 2.5^ (+.8)
a 2 (fraction) .42^ (-+.^ 03)^.^16 (+-. 04) k 2 (day-l)^ .015 (-+.006) .031 (^) (-+.04)
a 3 (fraction).^30 (-+. 04) k 3 (day-1) (^) .00063 (+. 0003)
a 4 (fraction) k 4 (day"l)
4 Components
. is (+-. 06) .11 (-+. o5) . i I (+-. 03) ¯ 0074 (+-.004)
.16 (+-. 07) .00036 (±. 0002)
- Average (+- t standard deviation)
I~L"0 200 i^ 400 I^ 600 I^ 800 I^ .....^ tO00I DAYS POST-EXPOSURE
Figure I. Whole-body retention of 90St following inhalation of 90SRC12.
DOSIMETRY
Cumulative average absorbed ~ radiation doses to the skeleton of each exposed dog in the90Sr
longevity study have been made using the relationship derived in last year’s Annual Report (p. 6):
- (^457) oA t Absorbed ~ dose (rad) (^) W (^) o 1 SB(t) (2)
Where A = O initial body burden of 90Sr in~±Ci W = total body weight in kg SB(t) = average skeletal burden at timet expressed as a fraction of the initial body burden The following assumptions have been made in deriving and using equation (Z): (a) skeletal weight -- 0. 1 W (b) W remained constant throughout the observation period (c) SB(t) could be adequately expressed as the whole-body retention minus the first or early clearance component Future calculations will incorporate some provisions for a changing body and skeletal weight with increasing time post-inhalation. Since most of the retained body burden of 90St is deposited in the skeleton, assumption (e) should be sufficiently accurate for this purpose. With the above assumptions and a calculation of the [3 radiation dose average over the dog’s entire skeleton, it is apparent that the resulting calculated doses are only approximate. In spite of this, they serve as useful relative comparisons among dogs exposed to different levels of 90Sr. In Table Z, the 48 exposed dogs are ranked on the basis of their retained ~Ci90Sr/kg at 14 days post-inhalation. Cumulative average absorbed ~ doses to the skeleton forthe first 32 and 365 days post-inhalation are also listed for each dog. Note that the 14-day ucig0sr/kg values serve as a good indicator of the relative ranking of the absorbed ~ radiation doses for these two time periods. The initial radiation dose rate, the radiation dose rate at death, and the cumulative radiation dose to time of death for bone are shown in Table 3 for dogs that have died or were euthanized. The cumulative radiation dose to skeleton for the six dogs that died or were euthanized at 18 to 31 days post-inhalation ranged from 670 to 1300 rads. The death of these dogs appeared to be due to hematologic dyscrasia; therefore, the radiation close of real significance is that delivered tothe bone marrow, a dose that is lower than that noted for skeleton.
CLINICAL OBSERVATIONS During the past year clinical abnormalities have been noted in l0 90St dogs and four control dogs. Two dogs, 195B and 195C, ranked fifth and sixth in the longevity study on the basis of their retained 90Sr burden at 14 days post-inhalation, died at Z8 and Z0 days, respectively, post-inhala- tion. Both dogs exhibited hematologic changes, clinical signs, and terminal pathology similar to that described in detail earlier (1966-1967 Annual Report, pages 1-18) for six dogs that had died previously at short time intervals following inhalation of large quantities of 90St. Animal Z3C, ranked llth in the longevity study on the basis of 14-day 90St burden, was noted at 1035 days post-inhalation to have a small firm mass on the costochondral junction of the 8th to 12th rib on the right side. At 1050 days post-inhalation, the mass had increased in size to 7.
cm anterior to posterior and 6.0 cm dorsal to ventral and was elevated from the body surface 3.
ca. The animals had pyrexia, accompanied by anorexia, sporadically from 1050 days until 1099
days post-inhalation.Radiographicexamination at 1051 days post-inhalationrevealed erosion of
the 9th rib on the right side. By 1092 days post-inhalation,the mass had enlarged to 16 cm ante-
rior to posterior, I0 cm dorsal to ventral and was elevated 6 cm from the body surface. At 1099
days post-inhalation,the animal was euthanizeddue to debilitatedcondition. The dog’s terminal
weight was 7.3 kg as contrastedwith 9.0 kg prior to onset of the condition.
Animal IZF, ranked 14th in the longevity study on the basis of 14-day whole-body burden,
showed alarge swelling involving the deep tissues located dorsal to the sacroiliac junction just
left of the midline at 974 days post-inhalation. It had a slight lameness of the left hind leg. On
radiographic examination at 975 days post-inhalation there was irregular erosion of bone and de-
position of bone on the anterior aspect of the proximal end, including the ilial crest, ilium^ and
adjacent sacrum. Alarge area of soft tissue swelling was dorsal to the bone lesion. A small
calcium body was present anterior to the joint capsule. No fractures were seen. At 1003 days
post-inhalation, the area adjacent to the left sacroiliac articulation was more decalcified than on
previous examinations. At 1018 days post-inhalation, radiographic examination showed osseous
involvement including bone erosion throughout nearly the entire ilium with spontaneous fracture of
the body. On radiographic examination at 1038 days post-inhalation, erosion of the bone of the
ilium appeared to be still more extensive. Anorexia was sporadic from 1004 days post-inhalation
until time of death. There was transient partial paresis of the hind quarters from 975 days post-
inhalation until the animal was euthanized in a debilitated condition at 1046 days post-inhalation.
The dog’s terminal weight was 6.4 kg as contrasted to 8.9 kg prior to onset of disease.
Animal 7B, ranked second in the sacrifice study on the basis of 14-day 90Sr burden, was ob-
served at 884 days post-inhalation to have bilateral abnormalities in the area of the costochondral
junction of the posterior ribs. On radiographic examination, an abnormal costochondral junction
of the posterior ribs was noted bilaterally along with achondroplasia of the long bones. The ani-
mal was observed at 900 days post-inhalation to have symptoms similar to cervical disc syndrome.
It exhibited pain and a nuchal rigidity on palpation. A radiographic examination performed 903
days post-inhalation revealed possible exostosis on the lateral mid-shaft of the right humerus.
Calcified discs at C7 and T1 were present with adjacent inflammation. At 905 days post-inhala-
tion, the animal had become lame in the right foreleg. Pain was present on palpation of the dor-
sal aspect of the neck. At 912 days post-inhalation, the animal began to show inappetence, andat
913 days post-inhalation had developed bilateral submaxillary edema and was still lame in the
right front leg. Partial radial nerve paralysis was present on this day. The animal had no ap-
petite after 924 days post-inhalation. Radiographic survey on day 924 showed soft tissue swelling
present in the area of the right humerus and scapula and a diffuse mass was present in the area of
the bifurcation of the trachea on the lateral view of the chest. There was an enlargement of the
costochondral junction of the posterior ribs that occurred bilaterally. The animal became more
lethargic and was euthanized 928 days post-inhalation due to severe debilitation.
Animal 10A, ranked fourth in the sacrifice study on the basis of 14-day 90Sr burden, was ob-
served radiographically at 1057 days post-inhalation to have an abnormality of the left greater tro-
chanter in the neck of the femur. Upon examination there was swelling of the deep tissues on the
anterior and lateral aspect of the scapula. The animal was carrying its left hind leg completely
flexed at 1077 days post-inhalation. Radiographic survey showed much erosion of the bone of the
neck and proximal end of the femur, and erosion of an area of the proximal end of the scapula. By
1114 days post-inhalatlon, the condition of the shaftof the femurhad rapidly deteriorated. At 1131
days post-inhalation, the enlargement over the scapula had grown to 10 cm anterior to posterior,
8 cm dorsal to ventral, and was elevated 3 cm from the surface of the thorax. Disuse atrophy was
present in all muscles of the left hind leg. At 1134 days post-inhalation, the dog started to again
place weight on his left rear leg. Radiographic examination at 1147 days post-inhalation revealed
that erosion of the neck, proximal shaft, and greater trochanter of the left femur had advanced.
There were probable metastases in the lung areas, particularly the left diaphragmatic lobe and
possibly the right cardiac lobe. The lesions in the left scapula appeared unchanged. At 1149 days
post-inhalation, the animal developed subcutaneous edema on the left ventral portion of the thorax
ventral to the mass associated with the left scapula. Radiographic examination at 1160 days post-
inhalation revealed a generalized infiltration in all lobes of the lungs except the right apical. New
bone lesions were noted on the wing of the right ilium at this time. The erosive lesion of the prox-
imal end of the femur involved all of the proximal third of the femur except the head. An area of
increased density was visible on the lateral chest exposure and appeared to be near the anterior
dorsal border of the right diaphragmatic lobe. Upon examination at 1161 days post-inhalation, the
mass dorsal to the left foreleg had increased in size and was increasing at a faster rate than pre-
viously. The animal had become weak and was losing weight. By 1168 days post-inhalation, the
animal had become progressively weaker and had a markedly elevated respiratory rate with harsh
tales present over the entire lung area. The mass dorsal to the left scapula was 9 cm from dor-
sal to ventral, 16 cm anterior to posterior and elevated 3 cm frornthe body surface. Radiographic
findings at 1168 days post-inhalation showed a destructive lesion involving the distal tip of the blade
and spine of the left scapula with a bony spicule extending into the soft tissue medially. On the
proximal end of the left femur, a large erosive lesion included the greater trochanter and part of
the femoral head. There was no radiographic evidence of extension of the tumor beyond the cor-
tex. Adestructive lesion of the right ilium near the crest was characterized by atarge cystic
area. Both lung fields were equally involved with radio-opacities as large as 2 cm in diameter
and less than a cm in diameter. Large lesions had confluent borders. There were possible areas
of atelectasis and possibly superimposed broncho-pneumonia in the left cardiac lobes with no evi-
dence of hydrothorax or pneumothorax present. The animal was euthanized at 1168 days post-
inhalation due to a severely debilitated condition.
Animal 9D, ranked sixth in the sacrifice study on the basis of 14-day 90St burden, was ob-
served at 1194 days post-inhalation to have developed a firm mass located at the costochondral
junction of the right 5th, 6th, and 7th ribs with dimensions of 2.5 cm anterior to posterior, 3.
cm dorsal to ventral and offset from the body 2.0 cm. There was no pain upon palpation. Radio-
graphic examination at 1194 days post-inhalation showed a large mass on the external rib cage
extending from rib 5 to rib 7 with no involvement of bone. At 1124 days post-inhalation, the ani-
mal was noted not placing any weight on its right leg. The lesion had not increased significantly
in size. At 1271 days post-inhalation, the mass in the right lateral external rib cagehad increased
to 6 cm in diameter. The animal continued to show lameness in the foreleg. The dog was still
alive at 1285 days post-inhalation (September 30, 1968}.
Animal 9C, ranked eighth in the sacrifice study on the basis of 14-day 90St burden, on radio~
graphic examination at 1057 days post-inhalation appeared to have an area of decalcificationin the
region of the right tibial tuberosity. At 1240 days post-inhalation, a firm mass was palpatable on
the medial aspect of the stifle joint. Radiographic examination this day showed the mass involved
the bone of the right tibia on the medial aspect. There was a fracture of the tibial crest. On ex-
amination at 1272 days post-inhalation, the mass on the proximal end of the right tibia had a swel-
ling which extended approximately halfway down the shaft. The diameter of the proximal end of
the tibia was approximately 6 cm. The animal would not use its leg. The dog was still alive at
1286 days post-inhalation (September 30, 1968).
All four dogs that developed angiosarcomaor osteochondrosarcoma had a similar hematologic
picture characterized by a moderate to marked anemia, and a leukocyte count that was normal to
elevated ranging from 13,000 to 39,000/ram 3 with amarked shift to the left so that granulocytes
comprised over 90% of theleukocytes. All had moderate to extreme extramedullaryhematopoiesis
in the liver and spleen and moderate to marked hyperplasia of gronulocytic elements in the mar-
row. In two cases, marrow smears contained tumor cells derived from the angiosarcoma.
CLINICAL CHEMISTRY
With the exception of four dogs that died or were euthanized with neoplastic disease, no pro-
found alterations in clinical chemistry values were noted.
Dogs 7B, 12F and 23C all showed an increase in serum levels of alkaline phosphase for ex-
tended periods of time prior to their death, an alteration consistent with the severe bone lesions
noted in these dogs. Similarly, these dogs and dog 10A all had some degree of reduction in serum
calcium levels. Metabolic involvement of liver and/or other tissues was suggested by marginally
lowered lactic acid dehydrogenase (12C), sporadically lowered albumin (12F), lowered blood
nitrogen and protein (7B), and elevated serum ghtamic aloacetic transmission (10A).
PATHOLOGY
Six dogs that have inhaled 90Sr died or were euthanized during the past year (Table 3). Path-
ologic changes noted in 195B and 195C were associated with severebone marrow damage andwere
identical to those described previously (1966-1967 Annual Report, page 1-18} for dogs that died
soon after inhalation of large quantities of 90St. The other four dogs were euthanized because of
tremors and their pathologic lesions will be described.
Three of these, 7B, 12F and 10Awere diagnosed ashaving angiosarcoma; the other (23C) was
diagnosed as having osteochondrosarcoma. In one case (7B)of angiosarcoma the tumor apparent-
ly arose in the right scapula, in a second case (10A) in the left scapula and in a third (1ZF) in
left ilium and sacrum. The two tumors attached to the scapulawere large and surrounded by athin
capsule. They projected into the axilla, impinged on the ribs and in one case into the neck slightly
displacing the trachea. The tumor invaded into the surrounding muscle, and tumor nodules ex-
tended into the subcutaneous tissues of the upper foreleg. Both tumors were firmly attached to
the inner surface of the scapula but did not invade the scapula or appear to arise from the bone of
the scapula. Grossly the tumors were soft, contained large areas of hemorrhage and necrosis and
smaller areas of yellow pigmentation. There were areas having a gray appearance which grossly
were thought to be viable tumor; these were most evident near the capsule. There was coarsely
lobular structure with the lobules being separated by septa. In both of these areas, there were
widespread distant metastases involving other bones, lungs, lymph nodes, spleen, liver, heart
and adrenals. Both cases also showed extramedullary hemopoiesis of the spleen and liver. In the
third case (12F) the angiosarcoma arose in the left ilium and sacrum and was accompanied by ex-
tensive destruction of the sacrum and ilium. There was a large retroperitoneal mass which did
not invade the peritoneum but partly displaced the rectum to the right, without showing any evi-
dence of obstruction. The urinary bladder was dilated and there was a rather marked bilateral
hydronephrosis; no obstruction to the urethra or ureters could be seen. The gross appearance was
essentially the same as that of the two tumors arising in the scapula. The only metastases from
this tumor were small microscopic ones in the lung and adrenal.
Microscopically these three tumors had the same structure. They consisted of masses of large ovoid or spindle shaped cells, with a large vesicular nucleus containing one nucleolus. In many areas there were spaces, frequently containing blood, lined by tumor cells (Figure 3). Fre- quently there were villus or papillomatous projections into these spaces. A similar structure was maintained in the metastases (Figure 4). The sections of the sacrum from animal 12F showed tu- mor growing around the nerves and sympathetic ganglia.
In animal Z3C, the tumor diagnosed asanosteochondrosarcoma arose in the right ribs, and showed partial destruction of two ribs. It was quite large weighing approximately 1200 gm. The tumor involved the intercostal tissues forminga fairly large subcutaneous mass and a larger mass that projected into the parietal pleura displacing the chest content to the left and the diaphragm downward. The tumor was encapsulated and did not invade the subcutaneous tissue or the lungs. It was firm in consistency, gray in color and contained areas of hemorrhage and necrosis.
The microscopic structure of the primary tumor varied somewhat in different areas. In some areas the tumor had an irregular lobular structure and the cells had an ovoid shape (Figure 5); these areas contained small loci of calcification. In other regions the cells were spindle shaped, growing in sheets and bands. They frequently contained calcification which produced irregular spicules of bone, many of which contained cells (Figure 6). Throughout the tumor there were loci of acellular eosinophilic material which had the structure of osteoid, and areas of primitive cart- ilage made up of large cells, many of which showed lacunae (Figure 7). Sections through the ribs that were partly destroyed revealed tumor surrounding the rib and invading the marrow cavity (Figure 8). The nuclei throughout this tumor were medium sized, vesicular and usually contain- ed a nucleolus. The cytoplasm was eosinophilic and varied in structure in different areas of the tumor. No gross microscopic metastases were found.
Figure 3 Section of angiosarcomaof scapula showing massesof tumorcells and sinuseslined by tumorcells. Fromdog 7B euthanized 928 days after inhalation and deposition of 130#Ci90Sr/kg. H+Estain, x125.
Figure 4 Section of metastasized angiosarcoma in spleen of dog 7B with masses of tumor cells and sinuseslined by tumorcells, the samestructure as the primary tumor. H+Estain, x125.
t
