Homografts of Bone Marrow in Dogs After Lethal Total-Body Radiation

Abstract

Abstract Twenty-two dogs (20 males and two females) were uniformly exposed over their entire surfaces to supralethal irradiation: 800 to 1,200 roentgens of 250 kv. x-rays measured in air at mid-body position. On the third day and after the last exposure, these irradiated animals were given infusions of normal bone marrow. The marrow for their infusions was taken from female litter-mates, from mothers or from unrelated dogs. Evidence for a return of marrow function and for a successful marrow graft was evaluated on the basis of: (1) the reappearance of formed elements: platelets, leukocytes, and reticulocytes, in the peripheral circulation; (2) the appearance in males of leukocytes bearing the sex-chromatin marker of the female donor; (3) prolonged survival, as compared to six irradiated control animals that were not given marrow; and (4) cellularity of marrow spaces and histologic evidence of marrow function at autopsy. It was found that marrow transplants usually succeeded after 800 to 1,200 roentgens of total-body irradiation when the infused marrow was taken from litter-mate sisters or from mothers (15 successes in 17 attempts). Marrow transplants between unrelated animals appeared more difficult but were not impossible. One success was obtained in five attempts, and this success was achieved with the coincidental use of splenectomy, ACTH and a large dose of marrow. Dogs with successful transplants lived longer than did control animals; in this series two to 10 times as long. When they died, they died of common canine infectious diseases and not of marrow failure. Distemper, hepatitis and leptospirosis, with or without superimposed bacterial respiratory disease, were the common causes of death. The lymph nodes and the splenic follicles of irradiated animals had, in most instances, not regained normal histologic appearance at the time of death from these infectious diseases. The working hypothesis is advanced that infusions of marrow repopulate marrow spaces in the canine after irradiation but are poor sources of the type of cell needed to restore lymphoid function and immunologic effectiveness in lymph nodes and spleen.