2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure of normal human dermal fibroblasts results in AhR-dependent and -independent changes in gene expression

Akintobi, A.; Villano, Caren M.; White, Lori A.

doi:10.1016/j.taap.2006.12.002

Cited by 30 publications

(20 citation statements)

References 52 publications

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“…Akintobi et al showed induction of cytochrome P450 1B1 (CYP1B1) expression in human dermal fibroblasts when exposed to xenobiotic substances like 2,3,7,8-tetrachlorodibenzo-p-dioxin [30]. Recent studies had shown that that CYP1B1, a newly identified member of the CYP1 family, plays a very important role in the metabolic activation of PAHs [31], [32].…”

Section: Discussionmentioning

confidence: 99%

Black Tattoos Entail Substantial Uptake of Genotoxicpolycyclic Aromatic Hydrocarbons (PAH) in Human Skin and Regional Lymph Nodes

et al. 2014

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Hundreds of millions of people worldwide have tattoos, which predominantly contain black inks consisting of soot products like Carbon Black or polycyclic aromatic hydrocarbons (PAH). We recently found up to 200 μg/g of PAH in commercial black inks. After skin tattooing, a substantial part of the ink and PAH should be transported to other anatomical sites like the regional lymph nodes. To allow a first estimation of health risk, we aimed to extract and quantify the amount of PAH in black tattooed skin and the regional lymph nodes of pre-existing tattoos. Firstly, we established an extraction method by using HPLC – DAD technology that enables the quantification of PAH concentrations in human tissue. After that, 16 specimens of human tattooed skin and corresponding regional lymph nodes were included in the study. All skin specimen and lymph nodes appeared deep black. The specimens were digested and tested for 20 different PAH at the same time.PAH were found in twelve of the 16 tattooed skin specimens and in eleven regional lymph nodes. The PAH concentration ranged from 0.1–0.6 μg/cm2 in the tattooed skin and 0.1–11.8 μg/g in the lymph nodes. Two major conclusions can be drawn from the present results. Firstly, PAH in black inks stay partially in skin or can be found in the regional lymph nodes. Secondly, the major part of tattooed PAH had disappeared from skin or might be found in other organs than skin and lymph nodes. Thus, beside inhalation and ingestion, tattooing has proven to be an additional, direct and effective route of PAH uptake into the human body.

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Section: Discussionmentioning

confidence: 99%

Black Tattoos Entail Substantial Uptake of Genotoxicpolycyclic Aromatic Hydrocarbons (PAH) in Human Skin and Regional Lymph Nodes

et al. 2014

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“…The AhR activators benz[a]anthracene andnaphtoflavone were shown to induce CYP1A1 mRNA and catalytic activity in human epidermal keratinocytes [209]. Similarly, induction of CYP1B1 in human dermal fibroblasts by TCDD was observed [210]. The cell-type specific up-regulation of CYP1A1 mRNA (>100 fold) and protein was observed in normal human keratinocyte cultures but not in dermal fibroblast cultures.…”

Section: Skinmentioning

confidence: 99%

Xenobiotic-Induced Transcriptional Regulation of Xenobiotic Metabolizing Enzymes of the Cytochrome P450 Superfamily in Human Extrahepatic Tissues

Pávek

Dvořák

2008

CDM

290

198

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Numerous members of the cytochrome P450 (CYP) superfamily are induced after exposure to a variety of xenobiotics in human liver. We have gained considerable mechanistic insights into these processes in hepatocytes and multiple ligand-activated transcription factors have been identified over the past two decades. Families CYP1, CYP2 and CYP3 involved in xenobiotic metabolism are also expressed in a range of extrahepatic tissues (e.g. intestine, brain, kidney, placenta, lung, adrenal gland, pancreas, skin, mammary gland, uterus, ovary, testes and prostate). Since the expression of the majority of the isoforms appears to be very low in the extrahepatic tissues in comparison with predominant expression in adult liver, the role of the enzymes in overall biotransformation and total body clearance is minor. However, basal expression and up-regulation of extrahepatic CYP enzymes can significantly affect local disposition of xenobiotics or endogenous compounds in peripheral tissues and thus modify their pharmacological/toxicological effects or affect absorption of xenobiotics into systemic circulation. The goal of this review is to critically examine our current understanding of molecular mechanisms involved in induction of xenobiotic metabolizing CYP genes of human families CYP1, CYP2 and CYP3 by exogenous chemicals in extrahepatic tissues. We concentrate on organs such as the intestine, kidney, lung, placenta and skin, which are involved in drug distribution and clearance or are in direct contact with environmental xenobiotics. We also discuss single nucleotide polymorphisms (SNPs) of key CYPs, which at the level of transcription affect expression of the genes in the extrahepatic tissues or are associated with some pathophysiological stages or disorders in the organs.

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“…For example, TCDD induces antiproliferative response of human breast cancer cells (MCF-7) [25] and reduction of p16 ink4a (a cell cycle regulator and tumor suppressor) in human dermal fibroblasts [26] independent of AhR. Recently, we have also revealed that AhR is not involved in mediating TCDD-inhibited angiogenic responses of human umbilical vein endothelial cells (HUVECs) [8].…”

Section: Introductionmentioning

confidence: 99%

ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR

Wang

Zou

et al. 2017

Reproductive Toxicology

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Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor is involved in regulation of many essential biological processes including vascular development and angiogenesis. 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an AhR ligand, which regulates immune responses and cancer cell growth. However, the roles of the ITE/AhR pathway in mediating placental angiogenesis remains elusive. Here, we determined if ITE affected placental angiogenic responses via AhR in human umbilical vein (HUVECs) and artery endothelial (HUAECs) cells in vitro. We observed that ITE dose- and time-dependently inhibited proliferation and viability of HUAECs and HUVECs, whereas it inhibited migration of HUAECs, but not HUVECs. While AhR siRNA significantly suppressed AhR protein expression in HUVECs and HUAECs, it attenuated the ITE-inhibited angiogenic responses of HUAECs, but not HUVECs. Collectively, ITE suppressed angiogenic responses of HUAECs and HUVECs, dependent and independent of AhR, respectively. These data suggest that ITE may regulate placental angiogenesis.

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure of normal human dermal fibroblasts results in AhR-dependent and -independent changes in gene expression

Cited by 30 publications

References 52 publications

Black Tattoos Entail Substantial Uptake of Genotoxicpolycyclic Aromatic Hydrocarbons (PAH) in Human Skin and Regional Lymph Nodes

Black Tattoos Entail Substantial Uptake of Genotoxicpolycyclic Aromatic Hydrocarbons (PAH) in Human Skin and Regional Lymph Nodes

Xenobiotic-Induced Transcriptional Regulation of Xenobiotic Metabolizing Enzymes of the Cytochrome P450 Superfamily in Human Extrahepatic Tissues

ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR

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