EXPERIMENTAL BONE MARROW REACTIONS : III. POLYCYTHEMIA, NORMOBLASTOSIS, AND ERYTHROCYTIC HYPERPLASIA OF THE BONE...

1. The effect produced by intravenous administration of gum shellac solution varied directly with the strength of the solution and the amount injected. (a) Strong solutions were intensely toxic and fatal to all the animals injected. Toxicity was abolished by the presence of carbon particles in the solution. (b) Medium strength solutions produced a marked normoblastosis followed by an erythroblastosis if injections were continued, accompanied either by an initial rise of red blood cells and hemoglobin followed by a decrease or an initial decline followed by an increase. The decrease of erythrocytes and hemoglobin did not amount to an actual anemia, and was usually concomitant with the greatest outpouring of nucleated red cells. (c) Small doses elicited the same kind of response except that the normoblastosis was less marked, the decrease of red cells and hemoglobin minimal or absent, the increase of red blood cells and hemoglobin marked in most instances. (d) Minimal doses elicited no appreciable reaction. 2. The bone marrow in animals killed after a course of injections showed intense erythrocytic hyperplasia. This disappeared after a variable length of time with a return of the bone marrow to apparently normal condition. 3. Toxic effects with non-fatal doses in form of hemorrhages were produced mainly in the bone marrow and occasionally in the kidney under the following conditions. (a) After one injection in an animal with hyperplastic marrow (hemorrhages ih the bone marrow only). (b) After the fourth and fifth dose when administered at long intervals (4 to 19 day intervals). (c) After one injection given 40 days after several successive injections (one animal only). 4. Small and divided doses administered at long intervals produced no apparent ill effect. 5. Subcutaneous administrations did not elicit any marked systemic reactions. Locally there was induration and edema. 6. The conclusion was drawn that gum shellac solution stimulates markedly the production of erythrocytes in the bone marrow. The mechanism of stimulation is not clear, but it seems unlikely that it is due to destruction of red blood cells in the peripheral blood stream.