Homologous Bone Marrow Transplantation in Dogs Receiving X-Radiation plus Urethan or 6-Mercaptopurine

Mongrel dogs were treated with 6-mercaptopurine (6-MP) or urethan prior to x-irradiation (900 r, delivered at a dose rate of 15 r/min.). The marrow dose was 7-11 x 10⁹ cells, given on the day following irradiation; urethan (175 or 350 mg./Kg.) and 6-MP (12.5 or 25 mg./Kg.) were administered at three or four daily intervals during the week prior to irradiation. Mean survival time (MST) in this group of 13 dogs was 23 days, with a maximum of 63 days. MST in a group of dogs given homologous marrow after 900 r, but not treated with the chemicals, was 10 days The treated animals characteristically showed good recovery of peripheral blood granulocyte count by 8-10 days, together with objective evidence of marrow "take"; recovery of mononuclear cell count was not observed, except in the single case which survived for 63 days. None of the control animals showed any rise in the peripheral blood count after initial depression, and all died with marrow aplasia. Secondary disease in treated dogs was characterized by anorexia, weight loss, infection, and lymphoid tissue aplasia in all the animals; skin atrophy, liver lesions, jaundice and anemia were seen in some of the animals. The marrow showed active hematopoiesis and moderate to good cellularity in most of the treated animals, although megakaryocyte activity was deficient in some. Pneumonia and pulmonary edema were found in many of the dogs at autopsy. It is evident that the use of these antimetabolites permits the successful transplantation of homologous marrow in dogs at a dose of x-radiation (900 r) which, by itself, is insufficient. These compounds (urethan and 6-mercaptopurine) are, therefore, additive to x-radiation with respect to suppressing the homograft reaction in dogs, as well as in rodents.