Prolonged Effects of Nitrogen Mustard on Mouse Haematopoietic and Lymphoid Tissues

Abstract

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 μg (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration from days 5–12. The thymus, lymph nodes, and spleen commenced regeneration during the second week post‐injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age‐matched controls from 20–30 d, 46–73 d, and 75–100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40–50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10–18 d post‐injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.