The effects of perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin on immune organs in rats

Citation
K. Nohara et al., The effects of perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin on immune organs in rats, TOXICOLOGY, 154(1-3), 2000, pp. 123-133
Citations number
33
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY
ISSN journal
0300483X → ACNP
Volume
154
Issue
1-3
Year of publication
2000
Pages
123 - 133
Database
ISI
SICI code
0300-483X(20001123)154:1-3<123:TEOPET>2.0.ZU;2-K
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is revealed to exert diverse bio logical effects including immunotoxicity, mainly by inadvertently activatin g the transcription factor arylhydrocarbon receptor (AhR). In the present s tudy, the developmental effects of perinatal exposure to low doses of TCDD on the major immune organs of offspring, thymus and spleen, were investigat ed focusing on weaning time (postnatal day (PND) 21), puberty (PND 49) and adulthood (PND 120) in male rats. Concurrently, TCDD contents in those orga ns were measured with a high-resolution gas chromatography-mass spectrometr y (GC/MS). In the thymus and spleen, CYP1A1 mRNA induction, the sensitive r eaction caused by activation of AhR, was also measured in order to examine whether perinatally administered TCDD call elicit gene expressions in these organs. When pregnant dams were administered a single oral dose of 12.5-80 0 ng TCDD/kg body weight on gestation day (GD) 15, the weights of the thymu s and spleen of the offspring did not differ from those of control animals throughout the experiments. The thymus and spleen maternally exposed to 800 ng TCDD/kg contained 102.0 and 62.7 pg TCDD/g tissue on PND 21, respective ly, and the amounts decreased thereafter. In the thymus, dose-dependent CYP 1A1 mRNA induction was clearly observed by maternal exposure to 50-800 ng T CDD/kg on PND 5. The induction was gradually decreased on PND 21 and 49. On the other hand, CYP1A1 mRNA induction in the spleen was very weak. In thes e thymi, no reproducible change was observed by TCDD exposure in cell numbe r and cellular population defined by CD4 and CD8 molecules at any time. In contrast, splenocyte number was shown to decrease by maternal exposure to 1 2.5-800 ng TCDD/kg in a dose-dependent manner on PND 49. The alteration in spleen cellularity by TCDD was not detected on PND 21 or 120, These results clarified that perinatal exposure to low doses of TCDD affects the immune organs, which is apparent in spleen around puberty and likely to be hardly relevant to AhR-dependent gene expressions. (C) 2000 Elsevier Science Irela nd Ltd. All rights reserved.