To better understand the role of the aryl hydrocarbon receptor (AHR) signaling pathway in causing tissue-specific signs of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in zebrafish, the temporal and spatial expression of the zebrafish aryl hydrocarbon receptor 2 (zfAHR2), aryl hydrocarbon receptor nuclear translocator 2 (zfARNT2), and an AHR regulated gene, cytochrome P4501A (zfCYP1A), w...

BACKGROUND: In the fish liver, the synthesis of egg yolk protein precursor vitellogenin (VTG) is under control of the estrogen receptor alpha (ERalpha). Environmental contaminants such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) are suspected to have antiestrogenic effects. The aryl hydrocarbon receptor (AHR) is the initial cellular target for TCDD and related compounds. The AHR is a ligand-...

The effects of treating female mice with single topical doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at various times before and after 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene, 3-methylcholanthrene (MCA), and (±)-trans7/S,8«-dihydroxy-9a,10a-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene were studied. TCDD, at doses of 1 /ig/mouse, was applied topically 3 days prior to, 5 min pri...

Halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (MC) cause transcriptional activation of the CYP1A1 gene via their interaction with the aromatic hydrocarbon (Ah) receptor. Direct radioligand binding and competitive binding studies demonstrated that the cytosolic Ah receptor from the mouse hepa...

This study was performed to determine whether TCDD (50 micrograms/kg; single oral dose) could induce adrenal microsomal lipid peroxidation, which might be correlated to decreased levels of cytochrome P-450 and 21-hydroxylase activity. The amount of malondialdehyde (MDA) formed was significantly higher than controls at days 1 through 5 following TCDD treatment. Microsomal cytochrome P-450 levels...

Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a ran...

2,3,7,8-Tetracholorodibenzo-p-dioxin is a highly toxic substance that can cause a variety of adverse effects on organisms. While it has been shown that TCDD acts mainly through the aryl-hydrocarbon receptor (AHR), the mechanism of toxicity is not completely clear. To test the role of the AHR in mediating the effects of TCDD, we exposed two congenic strains of mice differing only at the Ahr locu...

BACKGROUND 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association. OBJECTIVES On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential ex...

The present study of subchronic low exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at or near steady-state levels tries to emulate the most probable mode for human exposure, dietary consumption. This study is the first and most intensive pharmacokinetic study to be reported with repeated dosing, multiple times, and multiple doses examining disposition of TCDD-derived radioactivity and C...

The effective doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for inducing half-maximally (ED,, values) aryl hydrocarbon (benzolalpyrene) hydroxylase activity (EC 1.14.14.2) in H-4-11-E, Hepa-l, VERO, and HTC established cell culture lines are about 0.23, 0.45, 110, and >200 nM, respectively, and the maximally induced hydroxylase activity is more than 100 times higher in TCDD-treated H-4-11...