Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology

  title={Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology},
  author={Prabir Kumar Mandal},
  journal={Journal of Comparative Physiology B},
  • P. Mandal
  • Published 8 April 2005
  • Biology, Chemistry
  • Journal of Comparative Physiology B
A highly persistent trace environmental contaminant and one of the most potent toxicants known is dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin or TCDD). TCDD induces a broad spectrum of biological responses, including induction of cytochrome P-450 1A1 (CYP1A1), disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome, and cancer. Its classification was upgraded from “possible human carcinogen” (group 2B) to “human… 

TCDD Toxicity Mediated by Epigenetic Mechanisms

The potential role of epigenetic mechanisms in dioxins-induced cellular response is reported on by inspecting recent literature and focusing on epigenetic mechanism induced by the most toxic 2,3,7,8-TCDD.

AhR (Aryl Hydrocarbon Receptor) Polymorphisms: A Possible Role in TCDD (Dioxins)-AhR Binding and Carcinogenesis

A putative functional role of the intragenic AhR polymorphisms could greatly affect the functionality of the receptor by either inducing or contrasting its ligand-dependent activation, which may participate in lowering or increasing the risk of cancer, particularly, in the most polluted areas.

Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile

It is demonstrated that acute TCDD exposure results in immediate irregularities in the circulating and intestinal metabolome, which likely contribute to T CDD toxicity and can be used as biomarkers for the early detection of individual exposure.

Peganum harmala L. is a candidate herbal plant for preventing dioxin mediated effects.

It is concluded that Peganum harmala L. (Zygophyllaceae) fruiting tops to affect TCDD-activated AhR-mediated signal transduction in mouse hepatoma Hepa 1c1c7 cells can interfere with AhR ligands-mediated effects.

The Aryl Hydrocarbon Receptor: A Key Bridging Molecule of External and Internal Chemical Signals.

The aryl hydrocarbon receptor (AhR) pathway is a promising potential target for therapeutics targeting nervous, liver, and autoimmune diseases through AhR ligand-mediated interventions and other perturbations of AhR signaling.

Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier

It is shown that exposing isolated rat brain capillaries to 0.05–0.5 nM TCDD roughly doubled transport activity and protein expression of P-glycoprotein, an ATP-driven drug efflux pump and a critical determi-nant of drug entry into the CNS, and in situ brain perfusion indicated reduced brain accumulation of verapamil, a P- glycoprotein substrate.

Aryl hydrocarbon receptor-dependent induction of liver fibrosis by dioxin.

The AhR ligand, TCDD, induces hepatic fibrosis by directly regulating profibrotic pathways and it is confirmed that Snai2 is a direct transcriptional target of T CDD in the human hepatocarcinoma cell line, HepG2.



Functional role of AhR in the expression of toxic effects by TCDD.

Molecular biology of the Ah receptor and its role in carcinogenesis.

  • S. Safe
  • Chemistry, Biology
    Toxicology letters
  • 2001

Mechanisms of Ligand-Induced Aryl Hydrocarbon Receptor-Mediated Biochemical and Toxic Responses

Molecular mechanistic studies of TCDD action have contributed significantly to an improved understanding of the role of at least 2 bHLH/PAS proteins, as well as organ- and tissue-specific biochemical and toxic responses to this class of environmental toxins.

Animal models of human response to dioxins.

Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects, which is critical for assessing the risks to human populations under different circumstances of exposure.

Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity.

Results suggest that the pathological changes induced by TCDD in the liver and thymus are mediated entirely by the AHR, however, it is important to note that at high doses of T CDD, AHR-deficient mice displayed limited vasculitis and scattered single cell necrosis in their lungs and livers, respectively.

Dioxin and cancer: a critical review.

Immunological effects of chlorinated dibenzo-p-dioxins.

It is important for laboratory research to focus on defining TCDD-sensitive immunologic biomarkers in animal models that can also be used in human subjects to enable extrapolation of effects seen in laboratory animals to man.

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of cytochrome P450 1A1, the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor nuclear translocator in rat brain and pituitary.

Evidence is provided for the presence of CYP1A1, AHR, and ARNT in the central nervous system and in the pituitary, suggesting that TCDD may exert a direct effect on these regions.

Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.

  • S. Safe
  • Biology, Chemistry
    Pharmacology & therapeutics
  • 1995