C. Deheer et al., TIME-COURSE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)-INDUCED THYMIC ATROPHY IN THE WISTAR RAT, Toxicology and applied pharmacology, 128(1), 1994, pp. 97-104
Exposure to sublethal doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TC
DD) in Wistar rats results in thymic atrophy and reduced thymic cellul
arity. In a first experiment, rats were once orally intubated with 0,
1, 5, 25, 50, and 150 mu g TCDD/kg body wt and sacrificed at Day 10. T
he dose that produced one-half of the maximal thymic involution was es
timated at about 10-20 mu g/kg. The time course (Days 0-21) of thymic
atrophy induced by a single oral intubation of 25 mu g TCDD/kg body wt
revealed four phases. In phase 1 (initiation phase, Days 0-2) a decre
ase in proliferative activity was seen in cortical thymocytes, whereas
no changes occurred in thymic cellularity. Phase 2 (lymphodepletion p
hase, Days 2-8) was characterized by an initial strong depletion of im
mature CD4(+)CD8(+) double-positive (DP) cells (Day 4), followed by a
more gradual decrease in the number of mature thymocytes (Day 6). On D
ay 8 the lymphodepletion was maximal. In phase 3 (stationary phase, Da
ys 8-13) no changes occurred in thymic cellularity. Although the first
signs of recovery were already seen on Day 6, indicated by a recovery
in proliferative activity in the thymus cortex, an increase in thymic
cellularity was observed first after Day 13 (phase 4, recovery phase,
Day 13 onward). Reversibility of thymic atrophy is therefore observed
within the estimated half-life of TCDD in the rat thymus (>16 days).
We conclude that TCDD exerts a rapidly reversible effect on an intrath
ymic cortical target cell population. (C) 1994 Academic Press, Inc.