Homologous bone marrow transplantation in dogs receiving X-radiation plus urethan or 6-mercaptopurine.

By LEONARD J. COLE AND EDWARD L. ALPEN With the technical assistance of S. Maki and F. Lacina T HE DEMONSTRATION of the feasibility of homologous (i.e., genetically foreign ) bone marrow transplantation as a life-saving procedure in lethally x-irradiated rodents’3 has stimulated attempts to extend such observations to larger mammals such as dogs4’5 and monkeys,#{176} and also to man.7 In the case of dogs, in contrast to mice, it appears that exposure to doses several-fold larger than the LD50 does not suppress or abrogate the cellular systems involved in homograft rejection to the joint necessary for graft survival. This is indicated by the difficulty in obtaining successful homologous marrow transplants in this species.4’5’8 Thomas et al.5 have attempted to deal with this problem by splenectomizing the dogs 2 weeks before irradiation, giving high x-radiation doses ( 1200 r given in three daily exposures of 400 r each), and treating the irradiated recipients with ACTH. In more recent studies, Thomas et al.9 achieved some successful marrow homografts in dogs after exposure of the graft recipients to Co#{176}#{176} gamma radiation doses of 1200-1600 r at a dose rate of 4.2-4.4 r/min. Our present experiments on homologous bone marrow transplantation in x-irradiated dogs were designed to test whether transplantation would be more readily attained when x-radiation was combined with antimetabolites known to depress the immune response. The two antimetabohites investigated were 6-mercaptopurine ( 6-MP ) , and urethan. Schwartz and Dameshek1#{176} had first reported that 6-MP suppresses humoral antibody production in the rabbit; and that this compound could induce immunologic tolerance to punfled protein antigens. Meeker et al.’1 observed a definite prolongation of skin homograft survival in rabbits receiving 12 mg./Kg. of 6-MP daily for 14 days. Studies on mice in this laboratory12 have suggested that urethan in combination with x-radiation potentiates the inhibitory effect cf x-radiation on the homograft reaction in mice, although urethan did not by itself prolong the survival of skin homografts. A much earlier study on the effect of urethan on anaphylactic reactions was reported by Farmer.12”