Binding of a metabolite of 3,4,3′,4′-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin

This study aims to develop a rapid and sensitive cell-free bioassay of dioxins. It is known that dioxin ligand can bind heterodimeric aryl hydrocarbon receptor (AhR) and triggers the formation of the complex of dioxin-AhR, AhR nuclear translocator (ARNT), and dioxin-responsive element (DRE) region of the DNA. The hypothesis of the proposed method is that if FITC were labeled at the DRE sequence, its fluorescence intensity would be enhanced when the complex forms because the interaction interface of the binding components (AhR, ARNT, and DRE) creates a rather hydrophobic condition that is in favor of FITC emission. Effects of modification site of FITC on the DNA probes on binding efficiency between the complex components and fluorescence emission enhancement were evaluated by surface plasmon resonance and fluorescence analysis, respectively. Results showed that the labeling site at the second base at the 5′ end apart from the core region (5′-TNGCGTG-3′) of DRE did not obviously interfere with the binding between the DNA probe and dioxinAhR/ARNT hybrid but presented significant fluorescence emission enhancement. 2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD) was used as the typical toxin in this study. The method had a linear range of 1-100 pM, with detection limit of 0.1 pM (0.64 fg/assay) and coefficient of variation of 5.6% (n ) 10, 50 pM TCDD in transformed cytosol). The whole detection cycle was ∼4 h. The method was also used to estimate the toxic equivalents (TEQ) of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD) and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HxCDD). Measurement of TEQs of the mixture of TCDD, PeCDD, and HxCDD were highly consistent with the predicted data. The average recovery using fly ash extract was ∼93%.

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“…The nonplanar PCBs are AhR-independent and relatively low in toxicity without TEF values. 52,53 Our results are in accordance with the facts.…”

Section: Methodssupporting

confidence: 92%

Cell-Free Bioassay for Measurement of Dioxins Based on Fluorescence Enhancement of Fluorescein Isothiocyanate-Labeled DNA Probe

et al. 2006

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“…PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al, 1997), alter circulating hormone levels (Desaulniers et al, 1999), change patterns of estrous cyclicity (Meerts et al, 2004;Buitenhuis et al, 2004), disrupt hormone metabolism Kester et al, 2000;Yamane et al, 1975), influence endocrine-related and hypothalamic gene expression (Aluru et al, 2004;Bansal et al, 2005;Colciago et al, 2005;Flouriot et al, 1995;Gore et al, 2002;Pravettoni et al, 2005;Salama et al, 2003), interfere with hormone binding proteins (Brouwer and van den Berg, 1986;Chauhan et al, 2000), alter neuronal signaling to endocrine regions of the brain (Khan and Thomas, 2001;Morse et al, 1996;Seegal et al, 1985;Seegal et al, 1990) or indirectly affect steroid receptor availability via molecular crosstalk (Brunnberg et al, 2003;Pearce et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Steinberg

Juenger

Gore

2007

Hormones and Behavior

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Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the SpragueDawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. KeywordsAroclor 1221; Paced mating; PCB; Female reproductive behavior; Endocrine disruption Polychlorinated biphenyls (PCBs) were used in industry as inflammable coolants and lubricants and as components of paints and plastics. Banned in 1977 in response to dawning public awareness of their estrogenic and potentially toxic effects on humans and wildlife, PCBs continue to leach into soil, air and groundwater via retired industrial equipment, and from old factories and buildings. PCBs may have variable degrees of impact depending on which congeners or congener mixtures are involved, the organism's age at exposure, the sex of the individual, the degree of exposure and the availability of compensatory diet or social buffering to counteract those effects. An accurate evaluation of ecologically relevant xenobiotic exposure (Battershill, 1994;Brouwer et al., 1999).The neuroendocrine system serves as an interface between the central nervous system and peripheral endocrine organs, and thus represents a prime target for endocrine disruption by PCBs (Patisaul et al., 2006). PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al., 1997), alter circulating hormone levels (Desaulniers et al., 1999), change patterns of estrous cyclicity (Meerts et al., 2004;Buitenhuis et al., 2004), disrupt hormone metabolism Kester et al., 2000;Yamane et al., 1975), influence endocrine-related and hypothalamic gene expression ...

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“…Interestingly, metabolism of BDE-47 by phenobarbital-induced microsomes (mainly CYP2B) resulted in a strong increase in TTR binding, whereas β-naphthoflavone-induced microsomes (mainly CYP1A1) did not. Binding to TTR has been shown to be a general property for hydroxylated metabolites of PCBs and of other organohalogen compounds (123,129).…”

Section: Experimental Studies In Animalsmentioning

confidence: 99%

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

Darnerud

Eriksen

Johannesson

et al. 2001

Environ Health Perspect

685

263

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Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in plastics (concentration, 5--30%) and in textile coatings. Commercial products consist predominantly of penta-, octa-, and decabromodiphenyl ether mixtures, and global PBDE production is about 40,000 tons per year. PBDEs are bioaccumulated and biomagnified in the environment, and comparatively high levels are often found in aquatic biotopes from different parts of the world. During the mid-1970--1980s there was a substantial increase in the PBDE levels with time in both sediments and aquatic biota, whereas the latest Swedish data (pike and guillemot egg) may indicate that levels are at steady state or are decreasing. However, exponentially increasing PBDE levels have been observed in mother's milk during 1972--1997. Based on levels in food from 1999, the dietary intake of PBDE in Sweden has been estimated to be 0.05 microg per day. Characteristic end points of animal toxicity are hepatotoxicity, embryotoxicity, and thyroid effects as well as maternal toxicity during gestation. Recently, behavioral effects have been observed in mice on administration of PBDEs during a critical period after birth. Based on the critical effects reported in available studies, we consider the lowest-observed-adverse-effect level (LOAEL) value of the PBDE group to be 1 mg/kg/day (primarily based on effects of pentaBDEs). In conclusion, with the scientific knowledge of today and based on Nordic intake data, the possible consumer health risk from PBDEs appears limited, as a factor of over 10(6) separates the estimated present mean dietary intake from the suggested LOAEL value. However, the presence of many and important data gaps, including those in carcinogenicity, reproduction, and developmental toxicity, as well as additional routes of exposure, make this conclusion only preliminary. Moreover, the time trend of PBDEs in human breast milk is alarming for the future.

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Binding of a metabolite of 3,4,3′,4′-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin

Cited by 244 publications

References 25 publications

Cell-Free Bioassay for Measurement of Dioxins Based on Fluorescence Enhancement of Fluorescein Isothiocyanate-Labeled DNA Probe

Cell-Free Bioassay for Measurement of Dioxins Based on Fluorescence Enhancement of Fluorescein Isothiocyanate-Labeled DNA Probe

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

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