The specific protein-19S alpha-2 globulin, or <tex-math>$\alpha _{2}\text{-}{\rm MG}-\text{derived}$</tex-math> from human serum, which had previously been shown to antagonize some of the acute effects of radiation damage, is now shown to be capable of also inhibiting leukemogenesis by whole-body X-irradiation. Its action, both qualitatively and quantitatively, thus seems to be identical with that of <tex-math>$\alpha _{2}\text{-}{\rm MG}$</tex-math> derived from sheep spleen-the material mainly used in the earlier studies.

A single irradiation causes a rise in the haptoglobin level in the serum in mice, the level increasing with increase in the amount of radiation, up to doses near to lethal ones, at which the haptoglobin level diminishes. The amount of haptoglobin in the serum was smaller with fractionated doses of irradiation than with single doses. Endotoxin, or a protein fraction of human serum which contains the alpha-2 macroglobulin, increased the level of haptoglobin in both irradiated and nonirradiated mice.

Evidence is presented that the 19S alpha-2 globulin fraction, isolated from human serum or from sheep spleen, is capable of strongly enhancing regeneration of the mouse thymus damaged by radiation injury. This activity is preceded by enhancement of regeneration of the damaged bone marrow. The conditions for maximum activity of this protein fraction were studied in C57BL/6 mice submitted to four weekly irradiations of 170 R. Enhanced regeneration was obtained when each of the four injections of 19S alpha-2 globulin was given several hours before or after each irradiation, with a sharp optimum time of 2 hours before each irradiation. Increasing the number of injections beyond four did not achieve any demonstrable further increase in effect.

The increased level of hemoglobin in the bone marrow of mice, appearing after irradiation, is reverted by 19S alpha-2 globulin towards the normal level. The optimal conditions for this effect were found to be similar to those which produce stimulation of the regeneration of the thymus in irradiated mice. Injection of syngeneic bone marrow cells into irradiated mice produces a similar reversal of the increased level of hemoglobin in mice. A possible correlation between this effect of 19S alpha-2 globulin and its ability to regenerate irradiation damage in the bone marrow and thymus of mice is discussed.