Development of a Myeloproliferative Disorder in Beagles Continuously Exposed to 90

By D. L. DUNGwORTH, NI. GOLDMAN, J. W. SWITZER AND D. H. MCKELVIE T HE TERM “MYELOPROLIFERATIVE DISORDER” was introduced by 2 to embrace a complex array of diseases characterized by irreversible proliferation of one to several of the bone marrow cell lines, and includes such conditions as granulocytic leukemia, myelofibrosis with myeloid metaplasia, polycythemia vera and erythremic myelosis. The interrelationships among the various manifestations have been open to investigation only in human patients, and are still the subject of much debate. Spontaneous myeloproliferative disorders in domesticated animals are rare3’4 with the probable exception of the cat, and usually present as granulocytic leukemia. Until recently, therefore, when it was shown that beagles and miniature swine exposed continuously to 90Sr developed a myeloproliferative disorder,5 no animal analogy has been available for precise study. Whereas in beagles we have thus far observed only a myeloproliferative disorder,#{176} in swine both myeloproliferative and lymphoproliferative disorders have been reported. It has been known for some time that radiation is leukemogenic and that, in particular, bone-seeking radionuclides are effective in inducing leukemias in man and animals.8 Incidence rates of granulocytic and lymphocytic leukemias were increased in survivors of the Hiroshima and Nagasaki atomic bombing of World War II,#{176} and myelofibrosis with myeloid metaplasia has been observed occasionally.1#{176} Leukemias have also been noted with increased frequency in populations receiving accidental or therapeutic medical X-irradiation,” and myeloproliferative disorders have occurred in radium dial luminizers following ingestion of radium-paint mixtures.’2 When beagles are subjected to dietary exposure by #{176}#{176}Sr from mid-gestation to 1.5 years of age, a significant number of dogs on the higher dose levels have developed a myeloproliferative disorder which in its most active form presents as a granulocytic leukemia. More chronic cases resemble myelofibrosis with myeloid metaplasia (syn. agnogenic myeloid metaplasia). The purpose of this paper is to summarize our observations on beagles to date and to speculate