ToxSci Advance Access published online on January 12, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh048
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
* To whom correspondence should be addressed. E-mail: pnagark{at}hsc.vcu.edu.
Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes thymic atrophy, but the precise mechanism of such toxicity remains unresolved. The current study investigated the role of apoptosis in TCDD-induced thymic involution following perinatal exposure to TCDD. To this end, C57BL/6 pregnant mice were injected intraperitoneally on gestational day (gd) 14 with a single dose of 10 µg/kg TCDD. Analysis of the thymus on gd-15, gd-16, gd-17, gd-18 and on postnatal day (PD) 1, showed a remarkable reduction in thymic cellularity 3-7 days post-TCDD exposure. TCDD treatment also caused marked changes in the proportions of T-cell subsets, particularly on gd-17 and gd-18 thymocytes. In vitro culture of thymocytes from mice exposed perinatally to TCDD, showed increased apoptosis when compared to the controls, which peaked on day 3 post-TCDD exposure. Triple-color staining showed that TCDD induced apoptosis in all four subpopulations of T cells, with the double-positive T cells undergoing the highest level. Moreover, increased cleavage of caspase-3 was seen when TCDD-exposed gd-17 thymocytes were directly tested. Furthermore, apoptosis-associated phenotypic changes were found in thymocytes of mice perinatally exposed to TCDD, characterized by an increase in expression of CD3,
© 2004 Society of Toxicology
Immunotoxicology
Evidence for Induction of Apoptosis in T Cells from Murine Fetal Thymus Following Perinatal Exposure to 2, 3, 7, 8-Tetrachlorodibenzo-P-Dioxin (TCDD)
2 Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
Abstract 
TCR, IL-2R and CD44, and a decrease in CD4, CD8 and J11d markers. Finally, thymocytes from mice exposed perinatally to TCDD showed higher levels of Fas, TRAIL and DR5 mRNA, but the levels of Bcl-2, Bcl-xL and Bax were either unaltered or changed moderately. Taken together, these results suggest that TCDD-induced thymic atrophy following perinatal exposure may result, at least in part, from increased apoptosis mediated by death receptor pathway involving Fas, TRAIL and DR5.
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