2,3,7,8-tetrachlorodibenzo-p-dioxin Dotaz Zobrazit nápovědu
Podán je stručný přehled dosavadních znalostí o vzniku 2,3,7,8-tetrachlordibenzo-p-dioxinu, jeho výskytu v zevním prostředí, předpokládaném mechanismu účinku na živý organismus, o výsledcích experimentálních, klinických a epidemiologických studií. Přidány vlastní poznatky z mnohaletého sledování skupiny profesionálně intoxikovaných osob.
The author presents a brief review of hitherto assembled knowledge on the development of 2,3,7,8tetrachloro-dibenzo-p-dioxine, its incidence in the external environment, assumed mechanism of action on the living organism, on results of experimental, clinical and epidemiological studies. The author adds her own findings based on many years investigations of a group of subjects with occupati¬ onal intoxications.
- MeSH
- ekologie MeSH
- karcinogeny životního prostředí MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- teratogeny MeSH
- Publikační typ
- přehledy MeSH
The environmental contaminant 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) belongs to the category of highly toxic, persistent organic pollutants that accumulate in animal fat and plant tissues. Today, background TCDD levels in human fat are showing a decreasing trend. The food chain is the main source of exposure in the human population. TCDD regulates the expression of a wide range of drug-metabolizing enzymes and has an impact on a large number of biological systems. The most pronounced effects have occurred in occupational settings following the uncontrolled formation of TCDD after industrial accidents, as well as in rare intentional intoxications. Although the acute effects of TCDD exposure are well described in the literature, the long-term consequences have been underevaluated. The most well-known symptoms of severe acute intoxication are chloracne, porphyria, transient hepatotoxicity, and peripheral and central neurotoxicity. Because of the long-term persistence of TCDD in the human body, atherosclerosis, hypertension, diabetes, vascular ocular changes, and signs of neural system damage, including neuropsychological impairment, can be present several decades after massive exposure. Such chronic effects are nonspecific, multifactorial, and may be causally linked to TCDD only in heavily intoxicated subjects. This opinion is supported by the dose-dependent effect of TCDD found in exposed workers and by experimental animal studies.
- MeSH
- ateroskleróza chemicky indukované MeSH
- diabetes mellitus chemicky indukované MeSH
- financování organizované MeSH
- hypertenze chemicky indukované MeSH
- látky znečišťující životní prostředí toxicita MeSH
- lidé MeSH
- nemoci nervového systému chemicky indukované MeSH
- oční nemoci chemicky indukované MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The correlation between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication and the parameters of metabolic impairment was examined in the last eight male survivors of 80 workers exposed to TCDD during the production of herbicides in a chemical factory in 1965-1967. Their median TCDD blood level was 112 (46-390) pg/g lipids, and the median TCDD body deposit was 3.9 (0.8-11.7) μg. This puts these patients into the most severely intoxicated group of subjects, according to back-calculated levels of TCDD. The median TCDD blood level in eight controls was 12 pg/g (<0.10 to 22.2 pg/g). Markers of metabolic impairment - diabetes, dyslipidaemia, arterial hypertension, carotid artery plaque, skin microvascular reactivity, eye fundus hypertensive angiopathy and history of coronary heart disease - were assessed and compared to a general male population of comparable age. Measured parameters compared with a population of comparable age were as follows: prevalence of diabetes (62.5% versus 17.6%), arterial hypertension (87.5% versus 71.8%), dyslipidaemia (87.5% versus 88.8%), history of coronary heart disease (62.5% versus 26.0%) and eye fundus hypertension angiopathy (50% versus 14%). All eight patients (100% versus 43%) developed plaques in carotid arteries, six had stenosis >50% and two had a carotid intervention (stenting or endarterectomy). Total cholesterol levels decreased compared to the earlier study this patient group in 2008, most likely due to a more intensive use of lipid-lowering drugs. Several metabolic parameters were higher (diabetes as much as 3.5-fold) in the group of severely TCDD-intoxicated subjects than in a general population of comparable age. This suggests that TCDD plays a role in the development of metabolic impairment and vascular changes.
- MeSH
- diabetes mellitus epidemiologie etiologie MeSH
- herbicidy krev toxicita MeSH
- kardiovaskulární nemoci epidemiologie etiologie MeSH
- látky znečišťující životní prostředí krev toxicita MeSH
- lidé MeSH
- následné studie MeSH
- obsah radioaktivních látek v organizmu MeSH
- polychlorované dibenzodioxiny krev toxicita MeSH
- pracovní expozice škodlivé účinky MeSH
- prevalence MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
The aryl hydrocarbon receptor (AhR) activation has been shown to alter proliferation, apoptosis, or differentiation of adult rat liver progenitors. Here, we investigated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated AhR activation on a human model of bipotent liver progenitors, undifferentiated HepaRG cells. We used both intact undifferentiated HepaRG cells, and the cells with silenced Hippo pathway effectors, yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), which play key role(s) in tissue-specific progenitor cell self-renewal and expansion, such as in liver, cardiac, or respiratory progenitors. TCDD induced cell proliferation in confluent undifferentiated HepaRG cells; however, following YAP, and, in particular, double YAP/TAZ knockdown, TCDD promoted induction of apoptosis. These results suggested that, unlike in mature hepatocytes, or hepatocyte-like cells, activation of the AhR may sensitize undifferentiated HepaRG cells to apoptotic stimuli. Induction of apoptosis in cells with silenced YAP/TAZ was associated with upregulation of death ligand TRAIL, and seemed to involve both extrinsic and mitochondrial apoptosis pathways. Global gene expression analysis further suggested that TCDD significantly altered expression of constituents and/or transcriptional targets of signaling pathways participating in control of expansion or differentiation of liver progenitors, including EGFR, Wnt/β-catenin, or tumor growth factor-β signaling pathways. TCDD significantly upregulated cytosolic proapoptotic protein BMF (Bcl-2 modifying factor) in HepaRG cells, which could be linked with an enhanced sensitivity of TCDD-treated cells to apoptosis. Our results suggest that, in addition to promotion of cell proliferation and alteration of signaling pathways controlling expansion of human adult liver progenitors, AhR ligands may also sensitize human liver progenitor cells to apoptosis.
- MeSH
- adaptorové proteiny signální transdukční genetika MeSH
- apoptóza účinky léků genetika MeSH
- biologické modely * MeSH
- buněčné linie MeSH
- exprese genu účinky léků MeSH
- játra účinky léků patologie MeSH
- kmenové buňky účinky léků patologie MeSH
- lidé MeSH
- malá interferující RNA genetika MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- proliferace buněk účinky léků genetika MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- signální transdukce MeSH
- trans-aktivátory genetika MeSH
- transfekce MeSH
- transkripční faktory genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The last eight survivors of 80 workers accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during production of herbicides based on trichlorophenoxyacetic acid in 1965-1967 in a chemical factory were followed. All were men, mean age 72.4 ± 1.3 years. Their current median TCDD blood level was 112 (46-390) pg/g lipids. Neurological examination revealed central nervous system impairment in all individuals and signs of polyneuropathy in 87.5%, which was confirmed by a nerve conduction study (NCS) in 75%. A Lanthony test demonstrated acquired dyschromatopsia in 87.5% of the patients, with deterioration of mean colour confusion index (CCI) from 1.52 ± 0.39 in 2010 to 1.73 ± 0.41 in 2016. Single-photon emission computer tomography (SPECT) of the brain showed focal reduction of perfusion in various brain locations in all patients and worsening in six patients. Visual-evoked potentials (VEP) was abnormal in 62.6% of individuals. Most patients complained of psychological problems. The neuropsychological test battery showed most positive impairments in the Trail Making Test evaluating processing speed (average level in the range of mild neurocognitive impairment), which correlated with mean CCI (p < 0.05). CONCLUSION: Fifty years after exposure, blood levels of TCDD are still 10 times higher than the general population. NCS, VEP, Lanthony test and SPECT findings deteriorated from examination of these patients in 2004 and in 2010. The total of abnormal tests per patient in 2016 is very high. Minor differences among patients and their reduced count may explain why the number of impairments in 2016 does not correlate with TCDD blood level.
- MeSH
- časové faktory MeSH
- chemický průmysl * MeSH
- herbicidy škodlivé účinky krev chemická syntéza MeSH
- hygiena práce * MeSH
- jednofotonová emisní výpočetní tomografie MeSH
- kognice účinky léků MeSH
- lidé MeSH
- mozek diagnostické zobrazování účinky léků patofyziologie MeSH
- mozkový krevní oběh účinky léků MeSH
- nervové vedení účinky léků MeSH
- neurologické vyšetření MeSH
- neuropsychologické testy MeSH
- neurotoxické syndromy diagnóza etiologie patofyziologie psychologie MeSH
- perfuzní zobrazování metody MeSH
- polychlorované dibenzodioxiny škodlivé účinky krev chemická syntéza MeSH
- polyneuropatie chemicky indukované diagnóza patofyziologie MeSH
- pracovní expozice škodlivé účinky MeSH
- pracovní nehody * MeSH
- senioři MeSH
- vidění barevné účinky léků MeSH
- zrakové evokované potenciály účinky léků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Acta Universitatis upsaliensis. Comprehensive summaries of Uppsala dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 850
50 s. : il. ; 24 cm
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- infekční lékařství
- toxikologie
Problém s dioxinem začal v roce 1991, když U.S. Environmental Protection Agency (EPA) oznámila, že na základě nových vědeckých poznatků je nutné přehodnotit zdravotní riziko expozice 2,3,7,8 tetrachlorodibenzo-p-dioxinem (TCDD) a jemu chemicky podobným látkám, které označujeme jako dioxin. Tyto látky byly nalezeny ve všech kompartmentech životního prostředí a protože jsou velmi stálé a rozpouští se v tucích, mají schopnost akumulovat se v organismech vyšších živočichů - včetně člověka. . TCDD jako všudypřítomný polutant je vysoce toxický a představuje vážný zdravotní problém. Již velmi nízké koncentrace TCDD mohou mít negativní vliv na životní prostředí a lidské zdraví a nejvíce ohroženy jsou děti. Protože problém dioxinu je velmi často medializován a ne všechny informace o něm jsou správně vykládány, považujeme za nutné informovat zájemce o současných znalostech jeho biologické aktivity a zdravotního rizika.
The problem with dioxin began in 1991, when U.S. Environmental Protection Agency (EPA) announced that it would conduct a scientific reassessment of the health risks resulting from exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) and chemically similar compounds collectively known as dioxin. They are found in all environmental compartments, are persistent and, being fat soluble, they tend to accumulate in higher animals - including humans. TCDD like a ubiquitous pollutant is highly toxic and represents serious health problem. Even very small TCDD concentrations can cause negative effects on the environment and on human health, in particular on the most vulnerable groups like children. Since the problem of dioxin is published very often and not all of information is right interpreted, we treat necessary to inform interested persons about recent knowledge of its biological activity and health risk.
Past reports have correlated a diagnosis of porphyria cutanea tarda (PCT) with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Re-examination of the literature, however, has caused us to question the conclusion of a relationship between acquired PCT and TCDD. The major considerations at issue were: (1) whether the diagnostic label of PCT was applied excessively to cases with findings that are nonspecific; (2) whether the clinical conditions suggestive of PCT were the likely results of exposure to another chemical, for example hexachlorobenzene (HCB); and (3) whether a causal link between PCT and TCDD is reasonably substantiated by the facts. Based on the re-evaluation of the literature, the known effects of HCB and TCDD, and the follow-up results from the chemical plant, we submit that HCB alone, or HCB in combination with other polychlorinated aromatic hydrocarbons, may have been responsible for the effects observed and the subsequent correlation to PCT.
- MeSH
- dioxiny otrava MeSH
- dospělí MeSH
- kožní nemoci chemicky indukované epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci z povolání chemicky indukované epidemiologie MeSH
- polychlorované dibenzodioxiny otrava MeSH
- porfyrie chemicky indukované epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- Geografické názvy
- Československo MeSH
- New Jersey MeSH
Humic substances (HS) are ubiquitous natural products of decomposition of dead organic matter. HS is present in most freshwaters at concentrations ranging from 0.5 to 50mg L(-1). Organic carbon can represent 20% dry weight of sediments. Recently, the interaction of dissolved HS with the aryl hydrocarbon receptor (AhR) has been demonstrated. The AhR is a cytosolic receptor to which persistent organic pollutants (POPs) can bind and many of their toxic effects are mediated through interactions with this receptor. We describe in vitro effects (using H4IIE-luc cells) of binary mixtures of various HS with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), since in contaminated environments these compounds occur simultaneously. Six out of 12 HS samples activated AhR even at environmentally relevant concentrations (17 mg L(-1)), but did not reach the full AhR-activation even at excessive concentration. In simultaneous exposure of H4IIE-luc to HS (17 mg L(-1)) and TCDD (1.2 pM) without any preincubation prior to exposure, either significant additive or facilitative effects were observed. No negative interactions, due to possible sorption of TCDD to HS was observed. Nevertheless, if the HS-TCDD binary mixture was preincubated for 6 days prior to the exposure on H4IIE-luc cells, the additive and facilitative effects were less due to possible sorption of TCDD onto HS. Similar results were obtained from analogous experiments with greater concentrations of both TCDD and HS.
- MeSH
- huminové látky toxicita MeSH
- kinetika MeSH
- krysa rodu rattus MeSH
- látky znečišťující půdu toxicita MeSH
- nádorové buněčné linie MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- regenerace a remediace životního prostředí metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH