PMID- 14718643
OWN - NLM
STAT- MEDLINE
DCOM- 20041019
LR  - 20161124
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 78
IP  - 1
DP  - 2004 Mar
TI  - Evidence for induction of apoptosis in T cells from murine fetal thymus following 
      perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
PG  - 96-106
AB  - 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 microg/kg TCDD. Analysis of the thymus on GDs 15, 16, 17, and 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, 
      alphabetaTCR, 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.
FAU - Camacho, Iris A
AU  - Camacho IA
AD  - Department of Microbiology and Immunology, Medical College of Virginia Campus, 
      Virginia Commonwealth University, Richmond, Virginia 23298, USA.
FAU - Nagarkatti, Mitzi
AU  - Nagarkatti M
FAU - Nagarkatti, Prakash S
AU  - Nagarkatti PS
LA  - eng
GR  - AI 053703/AI/NIAID NIH HHS/United States
GR  - DA 014885/DA/NIDA NIH HHS/United States
GR  - DA016545/DA/NIDA NIH HHS/United States
GR  - ES 09098/ES/NIEHS NIH HHS/United States
GR  - F31ES11562/ES/NIEHS NIH HHS/United States
GR  - HL058641/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040112
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (DNA Primers)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Teratogens)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/genetics
MH  - CD8-Positive T-Lymphocytes/physiology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Separation
MH  - DNA Primers
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phenotype
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes/*drug effects
MH  - Teratogens/*toxicity
MH  - Thymus Gland/*cytology/*embryology
EDAT- 2004/01/14 05:00
MHDA- 2004/10/20 09:00
CRDT- 2004/01/14 05:00
PHST- 2004/01/14 05:00 [pubmed]
PHST- 2004/10/20 09:00 [medline]
PHST- 2004/01/14 05:00 [entrez]
AID - kfh048 [pii]
AID - 10.1093/toxsci/kfh048 [doi]
PST - ppublish
SO  - Toxicol Sci. 2004 Mar;78(1):96-106. doi: 10.1093/toxsci/kfh048. Epub 2004 Jan 12.