Histologic changes occurring in the hemopoietic organs of albino rats after single injections of 2-chloroethyl vesicants; a quantitative study
Kindred, J.E.
Archives of Pathology 43(3): 253-295
1947
ISSN/ISBN: 0361-7017 PMID: 20295404 Document Number: 12909
In young adult albino rats given single intravenous injections of lethal doses of sulfur mustard and the nitrogen mustards the following major changes occurred in the circulating blood and the hemopoietic organs: (1) lymphopenia in all groups; (2) lymphopenia and neutropenia in the group given methyl-his(2-chloroethyl) amine; (3) reduction of the weight and the amount of the lymphoid tissue of the thymus, the cervical lymph nodes and the spleen, and (4) hypoplasia and hyperemia of the, femoral marrow. Tris (2-chloroethyl) amine caused the greatest lymphopenia and had the most degenerative effect on the lymphocytes of the thymus, the lymph nodes and the spleen. Next in order of toxicity were the ethylhis and methyl-bis (2-chloroethyl) amines, which produced almost identical degenerative effects on these organs. Sulfur mustard was least effective initially but caused terminal changes of the same degree as those produced by the nitrogen mustards. In the lymphoid organs the lymphoid tissue shrinks in volume because of the destruction of lymphocytes, the inhibition of mitosis of the medium-sized lymphocytes and the migration of lymphocytes which go into the blood stream. The reticulum cells of the lymphoid organs are not injured directly by the agents. These cells as fixed phagocytes ingest and digest the degenerated lymphocytes. It is believed that many of them perish from the exhaustion resulting from their unusual phagocytic activity. Regeneration of the lymphoid tissue begins on the third day after injection, in general, and is characterized by increase of number and mitotic activity of the medium-sized lymphocytes. It is believed that these cells arise from small lymphocytes which have escaped the toxic action of the agents. In adrenalectomized rats given intravenous injections of tris (2chloroethyl) amine the same degenerative changes occurred as were observed in the nonadrenalectomized rats. Hence it is believed that the damage done to the lymphocytes in the lymphoid organs of the vesicant-injured rats is caused by direct action of the agents. Further evidence for the theory that the nitrogen mustards act directly on the lymphocytes accrues from the in vitro study of fragments of thymus suspended in plasma and tris (2-chloroethyl) amine. In these preparations the lymphocytes showed the same karyorrhectic changes which characterized them in the lymphoid organs of rats given injections of vesicants. There is a general direct correlation between the decrease of the number of lymphocytes of the blood and the degeneration of the lymphoid organs. However, it is thought that the initial loss of lymphocytes of the blood stream results because the lymphocytes migrate through the degenerated epithelium of the intestine into the lumen. The bo-ne marrow reacted more slowly to the vesicants than did the lymphoid organs, but it became hypoplastic and hyperemic. There was some destruction of cells, particularly of the mature granulocytes. The most marked effects were the decrease of the number of mature granulocytes and the inhibition of the mitosis of myelocytes lasting one day. Regeneration of myelocytes began on the third day after injection, but their maturation was apparently inhibited except in the sulfur mustard group. The megakaryocytes seemed to suffer the least change of any of the hemopoietic cells. No phagocytes containing great masses of degenerated cells were seen in the bone marrow, and in this respect there was a difference between the degenerative changes of the lymphoid organs and those of the marrow. The degenerative changes of the hemopoietic organs as a whole resembled more closely those produced by roentgen rays than those caused by any other agents.
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