Short- and Long-Term Morbidity and Mortality in the Population Exposed to Dioxin after the "Seveso Accident".

Pesatori, Angela Cecilia; Consonni, Dario; Bachetti, Silvia; Zocchetti, Carlo; Bonzini, Matteo; Baccarelli, Andrea; Bertazzi, Pier Alberto

doi:10.2486/indhealth.41.127

Cited by 136 publications

(89 citation statements)

References 49 publications

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“…In addition, epidemiological studies have revealed a positive correlation between dioxin exposure and defects in immune, neurological and reproductive functions as well as cancer incidence (Pelclova et al, 2001;Baccarelli et al, 2002;Pesatori et al, 2003). However, the underlying mechanisms of these adverse effects of dioxin are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism

et al. 2006

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Environmental chemicals such as dioxin adversely affect immune, neurological and reproductive functions and have been implicated in cancer development. However, the mechanisms responsible for dioxin toxicity are still poorly understood. Here, we show that dioxin and related pollutants trigger a marked morphological change in epithelial cells that remodel their cytoskeleton to increase interaction with extra cellular matrix while loosening cellcell contacts. Furthermore, dioxin-treated cells show increased motility. These dioxin-mediated effects are mimicked by constitutive expression and activation of the intracellular dioxin receptor (aryl hydrocarbon receptor (AhR)). They correlate with activation of the Jun NH2-terminal kinase (JNK) and are reverted by treatment with a JNK inhibitor. Dioxin-induced effects occur 48 h post-treatment initiation, a time scale, which argues for a genomic effect of the AhR, linked to induction of target genes. This novel Ahr action on cell plasticity points to a role in cancer progression.

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Section: Introductionmentioning

confidence: 99%

Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism

et al. 2006

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“…A variety of human epidemiologic studies have suggested a link between TCDD exposure and cardiovascular morbidity following occupational exposure (Bertazzi et al, 1989;Flesch-Janys et al, 1995;Vena et al, 1998;Pesatori et al, 1998;Pesatori et al, 2003). Retrospective analysis of 1189 chemical plant workers exposed to dioxin and furans reported a highly significant 2.5-fold (95% confidence interval-1.3-4.7) increase in relative-risk of death from heart disease due to dioxin exposure (FleschJanys et al, 1995;Pelclova et al, 2002).…”

Section: Effects Of Tcdd Exposure On Development Ahr In Developmentmentioning

confidence: 99%

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

et al. 2005

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ᮀTCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic in either bacteria or most in vitro assay systems. They do so in spite of having repeatedly been linked to oxidative stress and to mutagenic and carcinogenic outcomes. Oxidative stress, on the other hand, has been used as a marker for the toxicity of dioxin and its congeners. We have focused this review on the connection between oxidative stress induction and the toxic effects of fetal and adult dioxin exposure, with emphasis on the large species difference in sensitivity to this agent. We examine the roles that the dioxin-inducible cytochromes P450s play in the cellular and toxicological consequences of dioxin exposure with emphasis on oxidative stress involvement. Many components of the health consequences resulting from dioxin exposure may be attributable to epigenetic mechanisms arising from prolonged reactive oxygen generation.

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“…One of the most consistently identified diseases that were associated with TCDD exposure is the Type 2 diabetes mellitus [54][55][56]. Similar observations were also made in epidemiologic studies of other human subjects that were exposed to higher levels of TCDD [57][58][59][60]. However, the mechanism by which TCDD causes human Type 2 diabetes is not understood.…”

Section: Effect Of Tcdd and Hf Diet On Animal Body And Organ Weightmentioning

confidence: 81%

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin administration and high-fat diet on the body weight and hepatic estrogen metabolism in female C3H/HeN mice

Zhu

Gallo

Burger

et al. 2008

Toxicology and Applied Pharmacology

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We studied the effect of administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by i.p. injection once every two weeks in combination with a high-fat (HF) diet for 8 or 16 weeks on the body and organ weight changes as well as on the hepatic enzyme activity for estrogen metabolism in C3H/HeN female mice. Administration of TCDD at 100 μg/kg b.w. once every two weeks for 8 weeks increased the body weight by 46% in the HF diet-fed animals, but not in the regular diet-fed animals. This is the first observation suggesting that TCDD, a potent Ah receptor agonist, may have an obesity-inducing effect in animals fed a HF diet. While TCDD increased liver weight and decreased thymus weight in animals, these effects were enhanced by feeding animals a HF diet. Metabolism studies showed that TCDD administration for 8 or 16 weeks increased the liver microsomal activity for the 2-and 4-hydroxylation of 17β-estradiol in animals fed a control diet, but surprisingly not in animals fed a HF diet. Treatment with TCDD dose-dependently increased the hepatic activity for the O-methylation of catechol estrogens in both control and HF diet-fed animals, and it also decreased the levels of liver microsomal sulfatase activity for hydrolysis of estrone-3-sulfate. TCDD did not significantly affect the hepatic enzyme activity for the glucuronidation or esterification of endogenous estrogens. It is suggested that enhanced metabolic inactivation of 1 This study was supported, in part, by a grant from the American Cancer Society (RSG-02-143-01-CNE to BTZ) and also by grants from the NIH (CA92391, CA97109 and ES05022). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. endogenous estrogens by hepatic estrogen-metabolizing enzymes in TCDD-treated, control diet-fed animals contributes importantly to the reduced incidence of estrogen-associated tumors in animals treated with TCDD. NIH Public Access

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Short- and Long-Term Morbidity and Mortality in the Population Exposed to Dioxin after the "Seveso Accident".

Cited by 136 publications

References 49 publications

Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism

Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin administration and high-fat diet on the body weight and hepatic estrogen metabolism in female C3H/HeN mice

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