Some Properties of "rlp"--a Factor from Sheep Spleen Capable of Inhibiting Radiation Leukemogenesis in Mice.

FTER THE DISCOVERY that injection of syngeneic ( isologous ) bone marrow or spleen cells can antagonize both the acute lethal effectsl,2,a and the late leukemogenic effects4’5 of total body x-irradiation in mice, attempts to determine the mechanisms involved led to some conflicting conclusions.#{176}’7’8’9’10”1 As far as the acute lethal action of a single high dose of total body x-irradiation is concerned, the protective effect of injected bone marrow or spleen cells is generally believed to be dependent on the repopulation of certain vital cellular components of the hematopoietic system destroyed by the irradiation. Protection has, however, been obtained not only with syngeneic but also with allogeneic (homologous and heterologous) bone marrow’2”3”4 and spleen6 cells, and some degree of protection with cell-free extracts of spleen3’13’15’16”7 and even with protein-free18 and nucleoprotein#{176} fractions of such extracts. In the case of the long-delayed leukemogenic action of repeated, moderate doses of total body x-irradiation, only syngeneic tissues have been found to be effective for protection,19 whereas cell-free extracts have apparently not been tested for this system. Another aspect of radiation damage, which has incidentally served as a method of assay both for the degree of damage and the efficacy of protection against it, is the weight loss and recovery back to normal of the thymus. Thymus weight recovery was found to be stimulated by injection of normal bone marrow cells, or by their nuclei, but not by the supernatant fraction, following centrifugation of the suspension.5’2#{176} The responsible “factor” has been shown to be radiosensitive in vitro, not to he readily extractable with saline, and to be destroyed by freezing and lyophilization.2#{176} A number of important questions, arising from these observations, call for further investigation: (1) Are the mechanisms of protection against the acute lethal action, the early acceleration of thymic involution, and the late leukemogenic effect the same? (2) Does the evidence for cellular repopulation, in the case of protection against acute radiation damage, necessarily preclude the involvement of a cell-free (humoral) factor? (3) May not a humoral factor actually play a predominant role in the protection against radiation leukemogenesis, where the acute radiation damage is less severe, and consequently where cellular repopulation is not essential for survival? The conflicting interpretations of previous attempts to demonstrate humoral protective factors against radiation damage3’1’’3”5”6’17 may partly be ac-