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
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.