Kinetics of Changes, In Thymus and Other Lymphopoietic Organs of Adult Mice, Induced by Single Doses of Urethan<xref ref-type="fn" rid="FN2">2</xref>

The effects of a single dose of urethan (1.25 mg/g body weight) on the weights and histology of lymphoid organs and on the peripheral leukocytes were studied in young adult C57BL/6J mice. At 24 hours after urethan injection, the thymus decreased 38 percent in weight and showed marked cortical involution. The maximum weight loss (50%) occurred at 3 to 4 days, at which time the cortex was almost devoid of mature lymphocytes and consisted almost entirely of immature (large, rounded) cells. At 7 days, regeneration was advanced and the histological appearance was normal. The thymus returned to normal weight at 14 days but showed an overshoot in weight at 21 days. The spleen had comparable though less pronounced weight changes and a similar but more rapid pattern of recovery, accompanied by only a moderate decrease in cellularity. In both the thymus and spleen, signs of cell destruction were observed in only a few mice. These results suggest cell elimination as the mechanism of weight loss and rule out destruction in the spleen as accounting for the rapid and considerable decrease in the circulating leukocytes observed. The liver showed a slight transient rise in weight, while the weight of the testis did not change. AKR/Cu, SWR/J, and C3H/J mice also revealed thymic and splenic involution after treatment with urethan. Younger SWR/J mice showed a greater degree of lymphoid involution than older ones. These results are compared with observations suggesting that all leukemogenic systems depend on the persistence of immature thymic lymphocytes.