2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) role in hematopoiesis and in hematologic diseases: A critical review

Fracchiolla, Nicola Stefano; Annaloro, C.; Guidotti, Francesca; Fattizzo, Bruno; Cortelezzi, Agostino

doi:10.1016/j.tox.2016.10.007

Cited by 22 publications

(12 citation statements)

References 99 publications

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“…Hence, the major source of human exposure to dioxins is through diet, via consumption of meat, fish, and dairy products. While it is known that short-term and longterm exposures to dioxins affect human health, they can also transfer prenatally through the placenta, resulting in development of chronic diseases in later life [86]. However, influences through the paternal line are less documented.…”

Section: Dioxin and Dioxin-like Compoundsmentioning

confidence: 99%

Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals

et al. 2020

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Assessing long-term health effects from a potentially harmful environment is challenging. Endocrine-disrupting compounds (EDCs) have become omnipresent in our environment. Individuals may or may not experience clinical health issues from being exposed to the increasing environmental pollution in daily life, but an issue of high concern is that also the non-exposed progeny may encounter consequences of these ancestral exposures. Progress in understanding epigenetic mechanisms opens new perspectives to estimate the risk of man-made EDCs. However, the field of epigenetic toxicology is new and its application in public health or in the understanding of disease etiology is almost non-existent, especially if it concerns future generations. In this review, we investigate the literature on transgenerational inheritance of diseases, published in the past 10 years. We question whether persistent epigenetic changes occur in the male germ line after exposure to synthesized EDCs. Our systematic search led to an inclusion of 43 articles, exploring the effects of commonly used synthetic EDCs, such as plasticizers (phthalates and bisphenol A), pesticides (dichlorodiphenyltrichloroethane, atrazine, vinclozin, methoxychlor), dioxins, and polycyclic aromatic hydrocarbons (PAHs, such as benzo(a)pyrene). Most studies found transgenerational epigenetic effects, often linked to puberty-or adult-onset diseases, such as testicular or prostate abnormalities, metabolic disorders, behavioral anomalies, and tumor development. The affected epigenetic mechanisms included changes in DNA methylation patterns, transcriptome, and expression of DNA methyltransferases. Studies involved experiments in animal models and none were based on human data. In the future, human studies are needed to confirm animal findings. If not transgenerational, at least intergenerational human studies and studies on EDCinduced epigenetic effects on germ cells could help to understand early processes of inheritance. Next, toxicity tests of new chemicals need a more comprehensive approach before they are introduced on the market. We further point to the relevance of epigenetic toxicity tests in regard to public health of the current population but also of future generations. Finally, this review sheds a light on how the interplay of genetics and epigenetics may explain the current knowledge gap on transgenerational inheritance.

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Section: Dioxin and Dioxin-like Compoundsmentioning

confidence: 99%

Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals

et al. 2020

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“…The “dioxin receptor” was so-called because of its role in mediating the carcinogenic effects of the environmental contaminant 2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) [ 7 ]. The affinity of AHR for TCDD is extremely high, and the dissociation constant (K d ) for binding is in the order of picomolar concentrations of TCDD [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic dissection of endothelial transcriptional activity of zebrafish aryl hydrocarbon receptors (AHRs)

et al. 2017

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The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor conserved across phyla from flies to humans. Activated by a number of endogenous ligands and environmental toxins, studies on AHR function and gene regulation have largely focused on a toxicological perspective relating to aromatic hydrocarbons generated by human activities and the often-deleterious effects of exposure on vertebrates mediated by AHR activation. A growing body of work has highlighted the importance of AHR in physiologic processes, including immune cell differentiation and vascular patterning. Here we dissect the contribution of the 3 zebrafish AHRs, ahr1a, ahr1b and ahr2, to endothelial cyp1a1/b1 gene regulation under physiologic conditions and upon exposure to the AHR ligand Beta-naphthoflavone. We show that in fish multiple AHRs are functional in the vasculature, with vessel-specific differences in the ability of ahr1b to compensate for the loss of ahr2 to maintain AHR signaling. We further provide evidence that AHR can regulate the expression of the chemokine receptor cxcr4a in endothelial cells, a regulatory mechanism that may provide insight into AHR function in the endothelium.

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“…AHR-signaling is now known to participate in: cell migration (Mulero-Navarro and Fernandez-Salguero, 2016), epithelial cell development (Ikuta et al , 2009), cytoskeletal/adhesion regulation (Zhang et al , 2016), circadian rhythmicity (Anderson et al , 2013), barrier organ physiology (Esser and Rannug, 2015), cardiovascular and respiratory physiology (Sauzeau et al , 2011b), kidney development (Nanez et al , 2011), inner ear cochlear development in the neonate (Safe and Luebke, 2016), bone formation (Herlin et al , 2013) and osteoclastogenesis (Iqbal et al , 2013; Izawa et al , 2016), GI tract (Hubbard et al , 2015; Schiering et al , 2016), intestinal immunity (Qiu and Zhou, 2013), innate immunity (Cella and Colonna, 2015), hematopoiesis (Lindsey and Papoutsakis, 2012; Fracchiolla et al , 2016), transgenerational inheritance (Baker et al , 2014), reproductive organ development (Mulero-Navarro and Fernandez-Salguero, 2016), regulation of female reproduction (Hernandez-Ochoa et al , 2009), prostate gland development (Schneider et al , 2014), hyperlipidemia, atherogenesis, and hypertension (Xiao et al , 2014), thyroid-associated eye disease (Woeller et al , 2016), eye and ciliary body function (Shichi and Nebert, 1982; Volotinen et al , 2009), hepatic steatosis (Mellor et al , 2016), pancreatic beta-cell regulation (Sabatini and Lynn, 2015), glucose and lipid metabolism (Gooley, 2016), circadian clock and metabolic syndrome disruption (Jaeger and Tischkau, 2016), DNA damage control (Wells et al , 2010), tumor prevention by regulating gut immunity and growth suppression in tumor cells (Ikuta et al , 2016), and protection against oxidative stress (Wölfle et al , 2014). …”

Section: Ahr and Cell-signaling Pathwaysmentioning

confidence: 99%

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

Nebert

2017

Progress in Lipid Research

220

191

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The basic-helix-loop-helix Per-Arnt-Sim (bHLH/PAS) family comprises many transcription factors, found throughout all three kingdoms of life; bHLH/PAS members “sense” innumerable intracellular and extracellular “signals” — including endogenous compounds, foreign chemicals, gas molecules, redox potential, photons (light), gravity, heat, and osmotic pressure. These signals then initiate downstream signaling pathways involved in responding to that signal. The term “PAS”, abbreviation for “Per-Arnt-Sim” was first coined in 1991. Although the mouse Arnt gene was not identified until 1991, evidence of its co-transcriptional binding partner, aryl hydrocarbon receptor (AHR), was first reported in 1974 as a “sensor” of foreign chemicals, up-regulating cytochrome P450 family 1 (CYP1) and other enzyme activities that usually metabolize the signaling chemical. Within a few years, AHR was proposed also to participate in inflammation. The mouse [Ah] locus was shown (1973–1989) to be relevant to chemical carcinogenesis, mutagenesis, toxicity and teratogenesis, the mouse Ahr gene was cloned in 1992, and the first Ahr(−/−) knockout mouse line was reported in 1995. After thousands of studies from the early 1970s to present day, we now realize that AHR participates in dozens of signaling pathways involved in critical-life processes, affecting virtually every organ and cell-type in the animal, including many invertebrates.

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) role in hematopoiesis and in hematologic diseases: A critical review

Cited by 22 publications

References 99 publications

Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals

Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals

Genetic dissection of endothelial transcriptional activity of zebrafish aryl hydrocarbon receptors (AHRs)

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

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