The effects of perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin on immune organs in rats.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is revealed to exert diverse biological effects including immunotoxicity, mainly by inadvertently activating the transcription factor arylhydrocarbon receptor (AhR). In the present study, the developmental effects of perinatal exposure to low doses of TCDD on the major immune organs of offspring, thymus and spleen, were investigated focusing on weaning time (postnatal day (PND) 21), puberty (PND 49) and adulthood (PND 120) in male rats. Concurrently, TCDD contents in those organs were measured with a high-resolution gas chromatography-mass spectrometry (GC/MS). In the thymus and spleen, CYP1A1 mRNA induction, the sensitive reaction caused by activation of AhR, was also measured in order to examine whether perinatally administered TCDD can elicit gene expressions in these organs. When pregnant dams were administered a single oral dose of 12.5-800 ng TCDD/kg body weight on gestation day (GD) 15, the weights of the thymus 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, respectively, and the amounts decreased thereafter. In the thymus, dose-dependent CYP1A1 mRNA induction was clearly observed by maternal exposure to 50-800 ng TCDD/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 these thymi, no reproducible change was observed by TCDD exposure in cell number and cellular population defined by CD4 and CD8 molecules at any time. In contrast, splenocyte number was shown to decrease by maternal exposure to 12.5-800 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.
Nohara
K
K
National Institute for Environmental Studies, Environmental Health Sciences Division, Onogawa, Tsukuba, Ibaraki 305-0053, Japan.
Fujimaki
H
H
Tsukumo
S
S
Ushio
H
H
Miyabara
Y
Y
Kijima
M
M
Tohyama
C
C
Yonemoto
J
J
D000818:Animals; D000831:Animals, Newborn; D002850:Chromatography, Gel; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D008401:Gas Chromatography-Mass Spectrometry; D018507:Gene Expression Regulation, Developmental; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects* / Q000196:embryology; D013723:Teratogens / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects* / Q000196:embryology
D017931:DNA Primers; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D012313:RNA; D004247:DNA; D003577:Cytochrome P-450 Enzyme System