Disease relevance of Tetrachlorodibenzodioxin

• Keratinization of mouse teratoma cell line XB produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin: an in vitro model of toxicity [1].
• Excess mortality from all cancers combined, cancers of the respiratory tract, and soft-tissue sarcoma may result from exposure to TCDD, although we cannot exclude the possible contribution of factors such as smoking and occupational exposure to other chemicals [2].
• Mortality from several cancers previously associated with TCDD (stomach, liver, and nasal cancers, Hodgkin's disease, and non-Hodgkin's lymphoma) was not significantly elevated in this cohort [2].
• 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons produce epidermal hyperplasia, hyperkeratosis and sebaceous gland metaplasia in the skin of mice bearing the recessive mutation (hr/hr) hairless [3].
• Dioxin tied to endometriosis [4].

Psychiatry related information on Tetrachlorodibenzodioxin

• The prototype AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) did not affect the rates of chronic alcohol consumption in B6 or D2 mice, suggesting that dioxin-inducible metabolism does not play a major role in alcohol drinking preference [5].
• We found no indication of increased birth defect severity, delays in development, or hyperkinetic syndrome with paternal dioxin [6].
• This paper describes the use of geostatistical modeling approaches to quantify uncertainty of 2,3,7,8-tetrachlorodibenzo-p-dioxin concentrations in Passaic River (New Jersey) sediments and to incorporate this information in decision-making processes, such as delineation of contaminated areas and additional sampling needs [7].
• Treatment of male rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a dose-dependent decrease in body weight, feed intake, resting and total oxygen consumption, and spontaneous motor activity [8].
• Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial and visual reversal learning in rats [9].

High impact information on Tetrachlorodibenzodioxin

• The Ahr is also activated by dioxin, one of the most intensively studied environmental contaminants [10].
• Oocytes microinjected with a Bax promoter-reporter construct show Ahr-dependent transcriptional activation after PAH, but not dioxin, treatment, consistent with findings that dioxin is not cytotoxic to oocytes [10].
• This study of mortality among workers with occupational exposure to TCDD does not confirm the high relative risks reported for many cancers in previous studies [2].
• Our findings suggest a novel mechanism by which ER-mediated oestrogen signalling is modulated by a co-regulatory-like function of activated AhR/Arnt, giving rise to adverse oestrogen-related actions of dioxin-type environmental contaminants [11].
• PER contains a motif of approximately 270 amino acids whose function is unknown (termed PAS) and which is also present in three transcription factors of the basic-helix-loop-helix (bHLH) type, in the D. melanogaster single-minded gene product (SIM), and in both subunits of the mammalian dioxin receptor complex [12].

Chemical compound and disease context of Tetrachlorodibenzodioxin

• Despite its high TCDD content, soil from a contaminated area associated with a 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) manufacturing site in Newark, New Jersey, did not induce acute toxicity when administered to guinea pigs (the most sensitive species) by gavage [13].
• Promotion of N-nitrosodiethylamine-initiated hepatocellular tumors and hepatoblastomas by 2,3,7,8-tetrachlorodibenzo-p-dioxin or Aroclor 1254 in C57BL/6, DBA/2, and B6D2F1 mice [14].
• The inhibitory potencies of three dioxin congeners on adipose glucose transporting activities follows the same order of their toxicities in vivo [15].
• In contrast, the human dioxin receptor was not activated by omeprazole upon expression in a receptor-deficient mouse hepatoma cell line [16].
• The isozyme inducible in normal liver by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the tumor-specific isozyme found in hepatocellular carcinomas have apparent molecular weights of 110,000, prefer NADP+ as coenzyme, and preferentially oxidize benzaldehyde-like aromatic aldehydes, but not phenylacetaldehyde [17].

Biological context of Tetrachlorodibenzodioxin

• This difference in the action of PAHs versus dioxin is conveyed by a single base pair flanking each Ahr response element in the Bax promoter [10].
• The concomitant formation of the dioxin and the trichlorophenol during hydrolysis of sym-tetrachlorobenzene has lead to demands for restrictions on the use of 2,4,5-T and related herbicides [18].
• Control of cytochrome P1-450 gene expression by dioxin [19].
• Toxicology. Panel backs EPA dioxin assessment [20].
• Analysis of liver samples demonstrated low bioavailability of TCDD from this soil [13].

Anatomical context of Tetrachlorodibenzodioxin

• Five TCDD-responsive complementary DNA clones were isolated from a human keratinocyte cell line [21].
• Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor [22].
• The livers of Ahr-/- mice were reduced in size by 50 percent and showed bile duct fibrosis Ahr-/- mice were also nonresponsive with regard to dioxin-mediated induction of genes encoding enzymes that catalyze the metabolism of foreign compounds [22].
• Measuring 2,3,7,8-tetrachlorodibenzo-p-dioxin in adipose tissue provides a much improved index of exposure, an important advance for research studies evaluating the possible health effects of this compound [23].
• The dioxin and peroxisome proliferator-activated receptors: nuclear receptors in search of endogenous ligands [24].

Associations of Tetrachlorodibenzodioxin with other chemical compounds

• Carcinogenicity testing of herbicide 2,4,5-trichlorophenoxyethanol containing dioxin and of pure dioxin in Swiss mice [25].
• The white rot fungus Phanerochaete chrysosporium degraded DDT [1,1,-bis(4-chlorophenyl)-2,2,2-trichloroethane], 3,4,3',4'-tetrachlorobiphenyl, 2,4,5,2',-4',5'-hexachlorobiphenyl, 2,3,7,8-tetrachlorodibenzo-p-dioxin, lindane (1,2,3,4,5,6-hexachlorocylohexane), and benzo[a]pyrene to carbon dioxide [26].
• In 1971, sludge wastes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin were mixed with waste oil and sprayed on a dirt road at the Quail Run Mobile Home Park in Gray Summit, Mo [27].
• MDR-1 (also known as PGY1) was induced following administration of aflatoxin B1, 2-(acetylamino)fluorene (AAF), N-hydroxy-2-(acetylamino)fluorene, isosafrole, phenothiazine, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but not after phenobarbital or 7-hydroxy-2-(acetylamino)fluorene treatment [28].
• Experimental evidence shows testicular dysfunction and impaired spermatogenesis in laboratory animals exposed to phenoxy herbicides, dioxin, or tetracycline, and antibiotic used extensively in military working dogs in Vietnam [29].

Gene context of Tetrachlorodibenzodioxin

• Gestational exposure of Ahr and Arnt hypomorphs to dioxin rescues vascular development [30].
• Moreover, the Cyp1a1 and Cyp1a2 genes and the Nmo-1 gene are induced by tetrachlorodibenzo-p-dioxin in the cch/cch, cch/c14CoS, and c14CoS/c14CoS mice [31].
• Aryl hydrocarbon receptor-mediated transcription: ligand-dependent recruitment of estrogen receptor alpha to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive promoters [32].
• Using chromatin immunoprecipitation assays, we studied the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated recruitment of the aryl hydrocarbon receptor (AhR) and several co-regulators to the CYP1A1 promoter [32].
• Mechanism of action of a repressor of dioxin-dependent induction of Cyp1a1 gene transcription [33].

Analytical, diagnostic and therapeutic context of Tetrachlorodibenzodioxin

• In both animal and epidemiologic studies, exposure to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD) has been associated with an increased risk of cancer [2].
• We conducted a retrospective cohort study of mortality among the 5172 workers at 12 plants in the United States that produced chemicals contaminated with TCDD [2].
• Short-term toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals: effects, mechanisms, and animal models [34].
• Mechanistic analyses of cytochrome P4501A1 induction provide insights into ligand-dependent mammalian gene expression, basic helix-loop-helix/Per-Arnt-Sim protein function, and dioxin action; such studies also impact public health issues concerned with molecular epidemiology, carcinogenesis, and risk assessment [35].
• The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin, was measured in the adipose tissue of 39 persons with a history of residential, recreational, or occupational exposure in Missouri and in 57 persons in a control group [23].

References