In vitro prenatal developmental toxicity induced by some petroleum substances is mediated by their 3- to 7-ring PAH constituent with a potential role for the aryl hydrocarbon receptor (AhR)

Lenny Kamelia*, Laura de Haan, Hans B. Ketelslegers, Ivonne M.C.M. Rietjens, Peter J. Boogaard

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

To test the hypothesis that 3–7 ring polycyclic aromatic hydrocarbons (PAHs) are responsible for the prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS), the present study evaluates the PDT potency of DMSO-extracts of 7 heavy fuel oils (HFO), varying in their PAH content, and 1 highly refined base oil (HRBO), containing no aromatics, in the embryonic stem cell test (EST). All DMSO-extracts of HFO inhibit ES-D3 cell differentiation in a concentration-dependent manner and their potency is proportional to the amount of 3–7 ring PAHs they contain. All DMSO-extracts of HFOs also show aryl hydrocarbon receptor (AhR)-mediated activities, as tested in the AhR-CALUX assay. Contrarily, the HRBO-extract tested negative in both assays. Co-exposure of ES-D3 cells with selected DMSO-extracts of PS and the AhR-antagonist trimethoxyflavone, successfully counteracted the PS-induced inhibition of ES-D3 cell differentiation, confirming the role of the AhR in mediating the observed PDT of PS extracts in the EST. A good correlation exists when comparing the in-vitro with the in-vivo PDT potencies of the PS under study. Altogether, our findings corroborate the hypothesis that PS-induced PDT is caused by 3–7 ring PAHs present in these substances and that the observed PDT is partially AhR-mediated.

Original languageEnglish
Pages (from-to)64-76
Number of pages13
JournalToxicology Letters
Volume315
DOIs
Publication statusPublished - 15 Oct 2019

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Aryl Hydrocarbon Receptors
Polycyclic Aromatic Hydrocarbons
Petroleum
Toxicity
Dimethyl Sulfoxide
Fuel Oils
Residual fuels
Embryonic Stem Cells
Stem cells
Cell Differentiation
Assays
Oils
In Vitro Techniques

Keywords

  • Aryl hydrocarbon receptor
  • Embryonic stem cell test
  • Petroleum substances
  • Polycyclic aromatic hydrocarbons
  • Prenatal developmental toxicity
  • UVCBs

Cite this

@article{09b9314a53bb4f5ba4eeb05e3219fdf9,
title = "In vitro prenatal developmental toxicity induced by some petroleum substances is mediated by their 3- to 7-ring PAH constituent with a potential role for the aryl hydrocarbon receptor (AhR)",
abstract = "To test the hypothesis that 3–7 ring polycyclic aromatic hydrocarbons (PAHs) are responsible for the prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS), the present study evaluates the PDT potency of DMSO-extracts of 7 heavy fuel oils (HFO), varying in their PAH content, and 1 highly refined base oil (HRBO), containing no aromatics, in the embryonic stem cell test (EST). All DMSO-extracts of HFO inhibit ES-D3 cell differentiation in a concentration-dependent manner and their potency is proportional to the amount of 3–7 ring PAHs they contain. All DMSO-extracts of HFOs also show aryl hydrocarbon receptor (AhR)-mediated activities, as tested in the AhR-CALUX assay. Contrarily, the HRBO-extract tested negative in both assays. Co-exposure of ES-D3 cells with selected DMSO-extracts of PS and the AhR-antagonist trimethoxyflavone, successfully counteracted the PS-induced inhibition of ES-D3 cell differentiation, confirming the role of the AhR in mediating the observed PDT of PS extracts in the EST. A good correlation exists when comparing the in-vitro with the in-vivo PDT potencies of the PS under study. Altogether, our findings corroborate the hypothesis that PS-induced PDT is caused by 3–7 ring PAHs present in these substances and that the observed PDT is partially AhR-mediated.",
keywords = "Aryl hydrocarbon receptor, Embryonic stem cell test, Petroleum substances, Polycyclic aromatic hydrocarbons, Prenatal developmental toxicity, UVCBs",
author = "Lenny Kamelia and {de Haan}, Laura and Ketelslegers, {Hans B.} and Rietjens, {Ivonne M.C.M.} and Boogaard, {Peter J.}",
year = "2019",
month = "10",
day = "15",
doi = "10.1016/j.toxlet.2019.08.001",
language = "English",
volume = "315",
pages = "64--76",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier",

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TY - JOUR

T1 - In vitro prenatal developmental toxicity induced by some petroleum substances is mediated by their 3- to 7-ring PAH constituent with a potential role for the aryl hydrocarbon receptor (AhR)

AU - Kamelia, Lenny

AU - de Haan, Laura

AU - Ketelslegers, Hans B.

AU - Rietjens, Ivonne M.C.M.

AU - Boogaard, Peter J.

PY - 2019/10/15

Y1 - 2019/10/15

N2 - To test the hypothesis that 3–7 ring polycyclic aromatic hydrocarbons (PAHs) are responsible for the prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS), the present study evaluates the PDT potency of DMSO-extracts of 7 heavy fuel oils (HFO), varying in their PAH content, and 1 highly refined base oil (HRBO), containing no aromatics, in the embryonic stem cell test (EST). All DMSO-extracts of HFO inhibit ES-D3 cell differentiation in a concentration-dependent manner and their potency is proportional to the amount of 3–7 ring PAHs they contain. All DMSO-extracts of HFOs also show aryl hydrocarbon receptor (AhR)-mediated activities, as tested in the AhR-CALUX assay. Contrarily, the HRBO-extract tested negative in both assays. Co-exposure of ES-D3 cells with selected DMSO-extracts of PS and the AhR-antagonist trimethoxyflavone, successfully counteracted the PS-induced inhibition of ES-D3 cell differentiation, confirming the role of the AhR in mediating the observed PDT of PS extracts in the EST. A good correlation exists when comparing the in-vitro with the in-vivo PDT potencies of the PS under study. Altogether, our findings corroborate the hypothesis that PS-induced PDT is caused by 3–7 ring PAHs present in these substances and that the observed PDT is partially AhR-mediated.

AB - To test the hypothesis that 3–7 ring polycyclic aromatic hydrocarbons (PAHs) are responsible for the prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS), the present study evaluates the PDT potency of DMSO-extracts of 7 heavy fuel oils (HFO), varying in their PAH content, and 1 highly refined base oil (HRBO), containing no aromatics, in the embryonic stem cell test (EST). All DMSO-extracts of HFO inhibit ES-D3 cell differentiation in a concentration-dependent manner and their potency is proportional to the amount of 3–7 ring PAHs they contain. All DMSO-extracts of HFOs also show aryl hydrocarbon receptor (AhR)-mediated activities, as tested in the AhR-CALUX assay. Contrarily, the HRBO-extract tested negative in both assays. Co-exposure of ES-D3 cells with selected DMSO-extracts of PS and the AhR-antagonist trimethoxyflavone, successfully counteracted the PS-induced inhibition of ES-D3 cell differentiation, confirming the role of the AhR in mediating the observed PDT of PS extracts in the EST. A good correlation exists when comparing the in-vitro with the in-vivo PDT potencies of the PS under study. Altogether, our findings corroborate the hypothesis that PS-induced PDT is caused by 3–7 ring PAHs present in these substances and that the observed PDT is partially AhR-mediated.

KW - Aryl hydrocarbon receptor

KW - Embryonic stem cell test

KW - Petroleum substances

KW - Polycyclic aromatic hydrocarbons

KW - Prenatal developmental toxicity

KW - UVCBs

U2 - 10.1016/j.toxlet.2019.08.001

DO - 10.1016/j.toxlet.2019.08.001

M3 - Article

VL - 315

SP - 64

EP - 76

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -