Killing effect of rat bone marrow in sublethally irradiated LAF mice.

Radiation death of lethally irradiated mice can be prevented by postirradiation injection of isologous mouse bone marrow (IBM) (18, 14). Protection in terms of body weight recovery and longterm survival is generally excellent with such treatment. Subsequent studies with foreign bone marrow protection showed transplantation and repopulation of the donor's hematopoietic tissues in the irradiated host (7, 11, 15, ~4, 25, s 80). Thus, similar protection against radiation death is obtained by the postirradiation injection of heterologous rat bone marrow (RBM). In contrast to the recovery of mice given IBM treatment, mice receiving RBM characteristically show a secondary body weight loss and a high percentage of delayed deaths 8-6 weeks after this treatment (~, 8, 15). From these observations and immunologic studies of this problem, Makinodan and Gengozian concluded that the "foreign bone marrow reaction" in lethally irradiated RBM-treated mice was attributable to a delayed immunologic response of the irradiated host to the foreign transplant, which resulted in a chronic in vivo antigen-antibody reaction (8, 15). Additional studies corroborated this (4, 9, 10, 16, 18-~8, ~7). A subsequent elaboration of this hypothesis stated that the occurrence (treatment-time relation), severity (chronic or acute), and final effects (physical and metabolic) of such an in vivo antigen-antibody reaction would depend on the x-ray dose and the number of RBM cells injected (9). Thus, the radiation-induced injury, the transplantability of the foreign tissues in the host, and the rate and degree of recovery of the host's immune mechanism are functions of the x-ray dose. The amount of foreign bone marrow injected must be considered, however, if the dividing donor ceils are to be recognized as proliferating antigens participating in a dynamic in vivo antigen-antibody (host-immune mechanism) reaction. Under appropriate conditions, then, the optimum balance of antigen and antibody in vivo in such a system could conceivably result in an acute reaction, which, compounded with the radiation-induced injury, would lead to death. This was borne out in (CSH)< 101)F1 mice that had received a sublethal x-ray dose of 710 r (LDa0) and 140 )< l0 s RBM cells intravenously after x-radiation. Sixty mice thus treated died within 16 days after treatment (8). The importance of the bone marrow dose was made evident in another study (9) showing that a smaller number of cells (75 • 106) injected into (CSH • 101)F1 mice irradiated with 710 r did not yield 100 per cent mortality; survivors were negative for the iforeign transplant. Injection of a greater number of RBM cells (800 X 106) resulted in a survivor that was positive for the transplant. Further variation of both the x-ray dose and number of bone marrow cells injected provided additional support for the working hypothesis. This enhanced killing effect has also been reported by Trentin with CBA mice irradiated with 550 r and injected with (CB • CBA)F1 bone marrow (~9). Similar adverse effects among sublethally irradiated (430-650 r) CBA mice treated with homologous C57BL or heterologous RBM: have been noted by van Bekkum and Vos (1). Santos, Cole, and Roan, using LAF1 mice, gave x-ray doses ranging from 600 to 1000 r, followed by intravenous injection of 70 rag. of RBNI. Mortality did not increase among the sublethally irradiated mice injected with RBM (e6). However, a constant 70-rag. dose of RBM was used, and, as noted in the hypothesis presented earlier, the in vivo antigen-antibody reaction and its manifestations are a function of the x-ray and the bone marrow dose. The present report shows both the "nonkilling" and "killing" effect of RBM in sublethally irradiated LAF~ mice when a variation of the RBM dose is considered.