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decreased immunoresponsiveness in animals. One of the earliest clues of this effect emerged from a series of animal experiments by Hektoen and Corper (1920). They observed that dogs and rabbits experienced depressed antibody formation after intravenous and intraperitoneal (IP) exposure to sulfur mustard. The sulfur mustard had a restraining effect on precipitation and on lysis—two of the principal ways antibodies can inactivate invading foreign agents—and profoundly modified the leukocyte count of the blood in experimental animals.

This series of studies placed sulfur mustard in a class with other leukocytic toxins such as benzene, which has frequently been associated with myelotoxicity expressed as leukopenia, pancytopenia, anemia, and aplastic or hypoplastic bone marrow (Dean and Murray, 1991).

Later studies with rabbits demonstrated that the number of leukocytes increased immediately after inhalation exposure but later diminished morphologically. The polymorphonuclear basophil (a type of white blood cell) showed abnormal developments of the nucleus and dissolution of the granules. The lymphocytes, which produce acquired immunity, also showed degenerative changes (Hektoen and Corper, 1920).

Similar results were achieved in experiments in which the route of absorption was intravenous: polymorphonuclear basophils increased following injection and then diminished rapidly, apparently disappearing from the peripheral blood. Zimmerman (1942) reported that lymphocyte disintegration began within 5 hours of intravenous injection of sulfur mustard; within 24 hours most of the lymphocytes had disappeared.

Quantitative histologic investigation of the effects of intravenously injected sulfur and nitrogen mustard on albino rats suggested a decreased immunoresponsiveness, expressed as leukopenia, lymphopenia, and neutropenia (the disappearance of the respective blood cells), as well as hypoplasia and hyperemia of bone marrow. In the lymphoid organs, tissue decreased in volume because of the destruction of lymphocytes (Kindred, 1947). The author further noted that the bone marrow reacted more slowly to the mustards than did the lymphoid organs, but it became hyperplastic. There was some destruction of cells, particularly of the mature granulocytes that protect the body against invading agents by ingesting them (Kindred, 1949).

These data on the albino rat have been supplemented by studies showing that dogs exposed to sulfur and nitrogen mustard experience toxic effects on lymphoid organs and bone marrow. The results of this action were observed in the quantitative decrease of cells in the peripheral blood of poisoned animals. The extent of cellular intoxication was directly related to the amount of the mustard injected (Kindred, 1949). Spurr (1947) further elucidated the influence of mustard com-

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