A purebred female Beagle dog that had received 2,000 R of protracted whole-body γ-irradiation from 60 Co when 14 months old had hematologic changes consistent with a myeloproliferative disorder 3 years after the termination of radiation exposure. Peripheral blood and bone marrow findings during the 7-month period before death showed progressive anemia with increased numbers of platelets; immature granulocytes, monocytes and promonocytes. A period of partial remission occurred during which time the peripheral blood was aleukemic, although there was marked thrombocytosis and abnormal erythropoiesis which was evidenced by bizarre circulating nucleated red cells, anisocytosis, poikilocytosis and Howell-Jolly bodies. The dog had a terminal crisis with marked leukocytosis, most cells in the peripheral blood being bizarre monocytes and promonocytes. Tissues obtained at necropsy showed diffuse as well as focal infiltration of the spleen, liver, lymph nodes, heart, kidney and gastrointestinal wall with immature neoplastic cells resembling monocytes and monocytic precursors. The monocytic differentiation of the invasive cell population was confirmed by morphological, cytochemical, histological, ultrastructural and in vitro cell culture studies.
In the last 17 years, 55 of 2,125 (2.6%) purebred beagles maintained in a closed colony had urolithiasis. Males comprised 72.7% of the affected animals. All the uroliths except one set in the kidneys were in the urinary bladder, the urethra, or both. All uroliths were nearly pure magnesium ammonium phosphate hexahydrate. Partially inbred beagles had a 10.7% incidence of urolithiasis, compared to a 2.0% incidence in an outbred line.
A leukemia model in a large animal, analogous to human myelogenous leukemia, would be invaluable for not only leukemogenic studies, but also in the design of chemotherapeutic trials and supportive therapy. The incidence of spontaneous myeloid leukemia in most domestic animals, however, is quite low (15,17,26), and this disease rarely occurs in the dog (10).
One hundred and sixteen colony control dogs (purebred beagles) ranging in age from 56 to 4868 days at the time of sampling, were tested at various intervals over a 10-year period to determine the normal values of several serum constituents. The effects of sex and family line were also noted. With increasing age, serum glutamic-pyruvic transaminase, total protein, and cholesterol increased, whereas glucose, serum glutamic-oxalacetic transaminase, creatine phosphokinase, iron, alkaline phosphatase, and albumin decreased. Females had significantly higher levles of urea nitrogen, iron, and cholesterol than males. Males had significantly higher serum glutamic-pyruvic transaminase levels. The rate of increase in serum cholesterol with age was greater in males than in females. Males showed no age related changes in levels of urea nitrogen or iron, while the females showed decreasing levels. Significant differences in total protein and albumin were noted in dogs belonging to different family.
A high incidence of leukemia in adult beagle dogs was induced by continuous whole-body exposure to low doses of 60Co gamma irradiation. At 5, 10, and 17 R per 22-hr exposure day, 20 animals of 53 died of either myelogenous leukemia (15 of 20) or erythroleukemia (5 of 20); the latter occurred only at 5 R/day. Consistent preclinical changes occurred in the peripheral blood, including (1) a partial recovery from an initial severe leukopenia, (2) a prolonged accommodation-to-irradiation phase, and (3) marked oscillations in platelet values in the preleukemic period. In the terminal condition the dogs were severely anemic, thrombocytopenic, and commonly leukopenic. Peripheral blood buffy-coat preparations contained circulating “blast” cells and juvenile forms. Abnormal erythrocyte and platelet morphology was consistently present. The bone marrow was altered most severely; other organs showed variable degrees of leukemic infiltration and proliferation and loss of normal tissue architecture. The marrow was hyperplastic with little or no fat remaining. Differential marrow cell counts showed increased numbers of immature cell forms. Myeloid: erythroid (M:E) ratios ranged from 2.6:1 to 61.5:1 in the granulocytic leukemias, and 0.2:1 to 1:1 in the erythroleukemias. Juvenile leukemic cells (both circulating and tissue forms) displayed a number of distinctive cytologic features, including asynchronous patterns of nuclear–cytoplasmic maturation, increased incidence of nuclear clefts, coalescence of cytoplasmic granules, and bizarre arrangements of endoplasmic reticulum. These experimentally induced canine leukemias have many hematologic and cytologic features in common with both spontaneous and radiation-induced leukemias of man. Thus, they may provide a useful model for the study of human leukemia.
Lymphocytic orchitis occurs spontaneously in a closed colony of beagle dogs with an incidence of 32% among 69 untreated males over 1 year of age. This disease is genetically influenced as determined by an analysis of the ancestral composition of each animal. Orchitis is related in its occurrence to lymphocytic thyroiditis which has been previously described in this colony. The incidence of both diseases increases with increasing degrees of relatedness to three sibling progenitors of a partially inbred line which comprises a significant portion of the colony. Among the dogs that derived all of their genes from the three progenitors, 85% had lymphocytic thyroiditis and 65% had lymphocytic orchitis. The pathologic changes in the testes result in a significant reduction in testis size and weight as well as sterility or reduced fertility.