Evaluation of relative potencies of PCB126 and PCB169 for the immunotoxicities in ovalbumin (OVA)-immunized mice

Pan, Xiaoqing; Inouye, Kaoru; Ito, Tomohiro; Nagai, Haruko; Takeuchi, Yoko; Miyabara, Yuichi; Tohyama, Chiharu; Nohara, Keiko

doi:10.1016/j.tox.2004.06.024

Cited by 13 publications

(7 citation statements)

References 24 publications

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“…In our previous study, 20 g/kg TCDD suppressed the splenocyte number to 60% of the number in unexposed control mice 1 wk after immunization (27). The same dose of TCDD reduced the thymus weights to 40 -60% (44). The fact that a similar extent of suppression was observed in the thymus and spleen of the Tg mice indicates that the major portion of the effect of TCDD in these organs is attributable to AhR activation in the T cells.…”

Section: Ca-ahr Suppresses the Increase In Spleen Weight And Splenocymentioning

confidence: 75%

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

Nohara

Pan

Tsukumo

et al. 2005

The Journal of Immunology

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The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix-PER-ARNT-SIM superfamily. Xenobiotics, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, bind the receptor and trigger diverse biological reactions. Thymocyte development and T cell-dependent immune reactions are sensitive targets of AhR-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity. However, the exact role of the AhR in T cells in animals exposed to exogenous ligands has not been clarified because indirect effects of activated AhR in other cell types cannot be excluded. In this study, we generated transgenic (Tg) mice expressing a constitutively active mutant of AhR under the regulation of a T cell-specific CD2 promoter to examine AhR function in T cells. The mRNAs of the constitutively active mutant of AhR and an AhR-induced gene, CYP1A1, were expressed in the thymus and spleen of the Tg mice. The transgene expression was clearly detected in the thymocytes, CD4, and CD8 T cells, but not in the B cells or thymus stromal cells. These Tg mice had a decreased number of thymocytes and an increased percentage of CD8 single-positive thymocytes, but their splenocytes were much less affected. By contrast, the increase in number of T cells and B cells taking place in the spleen after immunization was significantly suppressed in the Tg mice. These results clearly show that AhR activation in the T-lineage cells is directly involved in thymocyte loss and skewed differentiation. They also indicate that AhR activation in T cells and not in B cells suppresses the immunization-induced increase in both T cells and B cells.

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Section: Ca-ahr Suppresses the Increase In Spleen Weight And Splenocymentioning

confidence: 75%

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

Nohara

Pan

Tsukumo

et al. 2005

The Journal of Immunology

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“…Even at relatively low doses, DLPCBs cause adverse health effects in both the developing and mature organs of animals and human beings. Many adverse effects, such as reproductive toxicity (Baldridge et al, ; Steinberg et al, ), neurotoxicity (Schantz, ), immunotoxicity (Yoo et al, ; Pan et al, ), cancers (Pavuk et al, ; Bunaciu et al, ), and developmental toxicity (Lindenau and Fischer, ; Kim and Cooper, ; Gutleb et al, ) have been documented. Exposure to DLPCBs and highly toxic 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD) produce a series of developmental syndromes in zebrafish embryos, characterized by induction of pericardial and yolk sac edema, heart malformation, spinal curvature, impaired lower jaw growth and disturbed cardiovascular circulation (Teraoka et al, ; Hill et al, ; Antkiewicz et al, ; Handley‐Goldstone et al, ).…”

Section: Introductionmentioning

confidence: 99%

Developmental toxicity, EROD, and CYP1A mRNA expression in zebrafish embryos exposed to dioxin‐like PCB126

Liu

Nie

Lin

et al. 2014

Environmental Toxicology

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Dioxin-like PCB126 is a persistent organic pollutant that causes a range of syndromes including developmental toxicity. Dioxins have a high affinity for aryl hydrocarbon receptor (AhR) and induce cytochrome P4501A (CYP1A). However, the role of CYP1A activity in developmental toxicity is less clear. To better understand dioxin induced developmental toxicity, we exposed zebrafish (Danio rerio) embryos to PCB126 at concentrations of 0, 16, 32, 64, and 128 μg L(-1) from 3-h post-fertilization (hpf) to 168 hpf. The embryonic survival rate decreased at 144 and 168 hpf. The fry at 96 hpf displayed gross developmental malformations, including pericardial and yolk sac edema, spinal curvature, abnormal lower jaw growth, and non-inflated swim bladder. The pericardial and yolk sac edema rate significantly increased and the heart rate declined from 96 hpf compared with the controls. PCB126 did not alter the hatching rate. To elucidate the mechanism of PCB126-induced developmental toxicity, we conducted ethoxyresorufin-O-deethylase (EROD) in vivo assay to determine CYP1A enzyme activity, and real-time PCR to study the induction of CYP1A mRNA gene expression in embryo/larval zebrafish at 24, 72, 96, and 132 hpf. In vivo EROD activity was induced by PCB126 at 16 μg L(-1) concentration as early as 72 hpf but significant increases were observed only in zebrafish exposed to 64 and 128 μg L(-1) doses (p < 0.005) at 72, 96, and 132 hpf. Induction of CYP1A mRNA expression was significantly upregulated in zebrafish exposed to 32 and 64 μg L(-1) at 24, 72, 96, and 132 hpf. Overall, the severe pericardial and yolk sac edema and reduced heart rate suggest that heart defects are a sensitive endpoint, and the general trend of dose-dependent increase in EROD activity and induction of CYP1A mRNA gene expression provide evidence that the developmental toxicity of PCB126 to zebrafish embryos is mediated by activation of AhR.

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“…Dioxin-like PCBs exert their toxicities by activating the AhR, a ligand dependent transcription factor, in a similar manner to that of the most toxic dioxin, TCDD. However, previous study showed that PCB169-liganded AhR behaves differently from TCDD-liganded AhR in immune cells [5] . PCBs induce liver cancer in rodents and possibly in humans [25] .…”

Section: Discussionmentioning

confidence: 92%

“…As PCBs are lipid soluble, humans can accumulate them in tissues [3] and such bioaccumulation causes human health concern [4] . It has demonstrated previously that PCBs, especially coplanar PCBs, can lead to multiple negative effects on health, such as liver damage [5] - [8] .…”

Section: Introductionmentioning

confidence: 99%

Effect of caffeic acid derivatives on polychlorinated biphenyls induced hepatotoxicity in male mice

Li¹,

Cao²,

Dai³

et al. 2014

J Biomed Res

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Chronic exposure to coplanar polychlorinated biphenyls (PCBs), a potent inducer of toxic reactive oxygen species (ROS), in the environment and food can cause liver diseases. It remains unknown whether caffeic acid derivatives (CADs) exerted protective effect on PCB-induced hepatotoxicity. We sought to evaluate the activities of 3 CADs on PCB169-induced oxidative stress and DNA damage in the liver. Male ICR mice were administered with 1 μmol/mL PCB169 at 5 mL/kg body weight for 2 weeks. The mice were given CADs by gastric gavage for 3 weeks. We found that PCB169 decreased the growth rate and reduced the levels of superoxide dismutase (SOD), glutathione (GSH) and GSH peroxidase (GPx). It increased the liver weight, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels and CYP1A1 activity in the liver tissues and plasma of mice (P<0.05). Pretreatment of mice with CADs restored the above parameters to normal levels. There was a synergistic protective effect between CADs in preventing MDA and 8-OHdG formation and inducing CYP1A1 and phase II metabolism enzyme (SOD, GPx) activities (P<0.05). In conclusion, PCB169 induced hepatotoxicity and pretreatment with CADs had synergistic protective effects on liver damage.

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Evaluation of relative potencies of PCB126 and PCB169 for the immunotoxicities in ovalbumin (OVA)-immunized mice

Cited by 13 publications

References 24 publications

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

Developmental toxicity, EROD, and CYP1A mRNA expression in zebrafish embryos exposed to dioxin‐like PCB126

Effect of caffeic acid derivatives on polychlorinated biphenyls induced hepatotoxicity in male mice

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