2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent, bioaccumulative and toxic contaminant widely distributed in the environment. Fishes are the most sensitive vertebrates to TCDD, especially during their early developmental stages. TCDD induces various toxic effects including yolk sac edema, craniofacial malformation and neural damage in developing fish embryos. However, the effects of ...

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces immunosuppression in humans and animals. However, the effect of TCDD on Th2-type immune responses such as allergic reactions has been unclear. Using NC/Nga mice that developed atopic dermatitis-like skin lesions with marked elevation in plasma of total IgE when bred under conventional conditions, we investigated the effects of a sin...

The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modula...

One of the most sensitive targets of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is the immune system. Many arachidonic acid (AA) metabolites are potent immunoregulatory molecules, and in other systems, TCDD has been shown to alter AA metabolism. Furthermore, the genes for cyclooxygenase (cox) contain a dioxin response element, suggesting that exposure to TCDD may directly alter cox levels and ...

In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Recent data suggest a dose-dependent elimination rate for TCDD. A physiologically based pharmacokinetic (PBPK) model, which uses a body-burden-dependent elimination rate, was developed previously in rodents to describe the pharmacokinetics of TCDD and has been extrapolat...

2, 3, 7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has adverse effects on reproduction, in part due to direct actions at the ovary. It is unclear whether effects are further mediated by glands that regulate ovarian function. We investigated whether effects of TCDD are mediated via the hypothalamic-pituitary axis. Hypothalamic and pituitary tissues were cultured in medium with and without TCDD. TCDD d...

A role for the aryl hydrocarbon receptor (AHR) pathway in vascular maturation has been implicated by studies in Ahr-null mice. In this study the hypothesis that activation of AHR signaling by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters common cardinal vein (CCV) development in the zebrafish embryo was investigated. The CCV is a paired vessel that grows across the yolk, connecting to the h...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in rodents. However, liver tumor incidence is increased by TCDD in female Sprague-Dawley rats but not male rats in chronic carcinogen bioassays. Our studies have investigated this finding by evaluating histological and biochemical parameters in a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats (intact...

Endothelial injury or dysfunction is an early event in the pathogenesis of atherosclerosis. Epidemiological and animal studies have shown that 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increases morbidity and mortality from chronic cardiovascular diseases, including atherosclerosis. However, whether or how TCDD exposure causes endothelial injury or dysfunction remains largely unkno...

OBJECTIVE Some studies suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may affect glucose metabolism and thyroid function. To further assess the relation between exposure to TCDD and endocrine function, data from the largest morbidity study of industrial workers exposed to TCDD were examined. METHODS A cross sectional study of workers employed > 15 years earlier in the man...