Distribution of dioxin receptors and metabolizing enzymes of 2,3, 7,8-tetrachlorodibenzo-p-dioxin exposure mice models

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HUANG Li(Laboratory Animal Center, Guangzhou Medical College, Guangzhou 510182, China)
LIU Han-ying(Laboratory Animal Center, Guangzhou Medical College, Guangzhou 510182, China)
QIU Jian-feng(Laboratory Animal Center, Guangzhou Medical College, Guangzhou 510182, China)
FENG Yuan-yu(Laboratory Animal Center, Guangzhou Medical College, Guangzhou 510182, China)
Journal Title:
Volume 16, Issue 05, 2010
Key Word:
Dioxin;Receptor protein;Immunohistochemistry;Tissue distribution;Reproductive toxicity

Abstract: Objective To investigate relationships between high sensitivity to toxicity in NIH mice during early pregnancy and level of receptors and metabolizing enzymes to 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and to elucidate whether the sensitivity is associated with the TCDD accumulation induced by metabolic activation in the uterus. Methods Liver, kidney and uterus tissues in mice models of toxicity exposure during the early pregnancy were collected and fixed. Distribution of the aryl hydrocarbon receptor (AhR), aryl hydrocarbon receptor nuclear translocator (ARNT) and cytochrome P4501a2 (Cyp1a2) was then determined by immunohistochemical staining. Results In unexposed mice, the tissues of liver, kidney and uterus, displayed weak-positive signal of AhR and Cyp1a2 in cytoplasma and strong-positive signal of ARNT in the nuclei. The positive signal of cytoplasma AhR in these three types of tissues was enhanced to varying degrees along with increasing dose of TCCD exposure. Exposure to 50 ng/L TCDD increased both the percentage of AhR-positive area in liver (18.038±3.0916,P<0.01)and uterus (8.8140±1.4574,P<0.01) and optic density of AhR signals(0.1143±0.0066,0.2399±0.0054, P<0.01 ), while no change was found in kidney tissues. With the same treatment, changes in Cyp1a2 were mainly manifested by significant increase in optic density of Cypla2 signals in liver (0.31112±0.0107, P<0.01 ), uterus (0.3152±0.0432, P<0.05) and kidney (0.3334±0.0168, P<0.05 ), while the optic density of positive ARNT signals in nuclei decreased significantly in liver (0.2458±0.006, P<0.01 )and uterus(0.2139±0.0253, P<0.01 ), was largely unchanged but associated with a translocation from nuclei to cytoplasma in kidney. Exposure to 100 ng/L TCDD resulted in enhanced AhR and Cyp1a2 positive signals in all the tissues examined, abolition of ARNT signals in liver and uterus,and traslocation of ARNT signal from nuclei to cytoplasma in the kidney. Conclusions The AhR and Cyp1a2 in liver, uterus and kidney induced by TCDD-like agents may show increasing percentage of signalpositive area along with higher dose of TCDD exposure. In contrast, ARNT signal is weakened and subsequently abolished in nuclei of liver and uterus cells, and displays a traslocation from nuclei to cytoplasma in the kidney. These findings indicate that liver and uterus may share the same TCDD-induced signaling pathway which activates the exogenous toxic agents and should be one of the factors causing sensitivity to TCDD during early pregnancy in mice.

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