2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) alters the endogenous metabolism of all- trans -retinoic acid in the rat

Schmidt, Carsten K.; Hoegberg, Pi; Fletcher, Nicholas; Nilsson, Charlotte B.; Trossvik, Christina; Håkansson, Helen; Nau, Heinz

doi:10.1007/s00204-003-0457-8

Cited by 47 publications

(10 citation statements)

References 77 publications

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“…TCDD alters the metabolism of all- trans- RA (Schmidt et al 2003), suggesting the linkage between ALDH6 and RARB in Figure 2. RARB has been shown to play a role in the inhibition of cellular replication (Sun et al 2000).…”

Section: Resultsmentioning

confidence: 99%

“…RA enters the nucleus, where it binds to two types of ligand-activated nuclear transcription factors, the RA receptors (e.g., RARB) and the retinoid X receptors. Several groups have hypothesized that changes observed in RA levels from dioxin exposures are mediated through increased metabolism of retinal to RA through retinal dehydrogenases or cytochrome P450s or both (Schmidt et al 2003). Using these data together with the known AhR gene battery, we developed a hypothetical gene interaction network (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…Two recent experiments address these issues to a limited extent. Schmidt et al (2003) examined RA levels and changes in expression of CRBP1 in male Sprague-Dawley rats and saw significant changes in RA levels in kidney, liver, and serum, and a marginal change in liver CRBP1 after 28 days. They did not examine any of the genes in the network shown in Figure 2, so it is difficult to compare directly with our results.…”

Section: Discussionmentioning

confidence: 99%

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Gene Interaction Network Suggests Dioxin Induces a Significant Linkage between Aryl Hydrocarbon Receptor and Retinoic Acid Receptor Beta

Toyoshiba¹,

Yamanaka²,

Sone³

et al. 2004

Environ Health Perspect

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Gene expression arrays (gene chips) have enabled researchers to roughly quantify the level of mRNA expression for a large number of genes in a single sample. Several methods have been developed for the analysis of gene array data including clustering, outlier detection, and correlation studies. Most of these analyses are aimed at a qualitative identification of what is different between two samples and/or the relationship between two genes. We propose a quantitative, statistically sound methodology for the analysis of gene regulatory networks using gene expression data sets. The method is based on Bayesian networks for direct quantification of gene expression networks. Using the gene expression changes in HPL1A lung airway epithelial cells after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin at levels of 0.1, 1.0, and 10.0 nM for 24 hr, a gene expression network was hypothesized and analyzed. The method clearly demonstrates support for the assumed network and the hypothesis linking the usual dioxin expression changes to the retinoic acid receptor system. Simulation studies demonstrated the method works well, even for small samples.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Gene Interaction Network Suggests Dioxin Induces a Significant Linkage between Aryl Hydrocarbon Receptor and Retinoic Acid Receptor Beta

Toyoshiba¹,

Yamanaka²,

Sone³

et al. 2004

Environ Health Perspect

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“…Retinoids in liver, serum, and kidney were analyzed according to Schmidt et al [32]. The polar retinoids 9- cis -retinoic acid (9- cis -RA), 13- cis -retinoic acid (13- cis -RA), 13- cis -4-oxo-retinoic acid (13- cis -4-o-RA), 9- cis -4-oxo-13,14-dihydro-retinoic acid (9- cis -4-o-13,14-dh-RA), all- trans retinoic acid (all- trans RA) and the apolar retinoids retinol and retinyl palmitate were extracted by a single liquid-extraction, separated from each other via solid-phase extraction using an aminopropyl phase, and then injected onto two different HPLC systems that were coupled with UV detection.…”

Section: Methodsmentioning

confidence: 99%

“…The limits of detection (LOD) for all- trans RA and 9c-4o-13,14-dh-RA were 0.7 and 1.0 pmol/g tissue, and 0.3 and 0.6 pmol/ml serum, respectively. Retinol and retinyl palmitate were separated on a J'sphere ODS-H80 (4.6×150 mm, 4 µm particle size) obtained from YMC (Schermbeck, Germany), and were detected at 325 nm [32]. The LOD for retinol and retinyl palmitate were 5.6 and 5.5 pmol/g tissue, and 4.2 and 4.2 pmol/ml serum, respectively.…”

Section: Methodsmentioning

confidence: 99%

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

et al. 2014

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PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.

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Vitamin A und Carotinoide

Nau

Stahl

2012

Vitamine Und Spurenelemente

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2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) alters the endogenous metabolism of all- trans -retinoic acid in the rat

Cited by 47 publications

References 77 publications

Gene Interaction Network Suggests Dioxin Induces a Significant Linkage between Aryl Hydrocarbon Receptor and Retinoic Acid Receptor Beta

Gene Interaction Network Suggests Dioxin Induces a Significant Linkage between Aryl Hydrocarbon Receptor and Retinoic Acid Receptor Beta

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

Vitamin A und Carotinoide

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