Novel polar AhR-active chemicals detected in sediments of an industrial area using effect-directed analysis based on in vitro bioassays with full-scan high resolution mass spectrometric screening

Cha, Jihyun; Hong, Seongjin; Lee, Jung-Hyun; Gwak, Jiyun; Mun-Gi, Kim; Kim, Taewoo; Hur, Jin; Giesy, John P.; Khim, Jong Seong

doi:10.1016/j.scitotenv.2021.146566

Cited by 19 publications

(17 citation statements)

References 86 publications

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“…AhR-, AR-, GR-, and ER-mediated potencies of REs and RP-HPLC fractions were measured using H4IIE- luc , , MDA-kb2, , and T47D-kb luc , bioassays following the methods of previous studies. The cell culture and experimental conditions are shown in Table S2.…”

Section: Methodsmentioning

confidence: 99%

“…Responses of bioassays were converted to percentages of maximum responses to benzo[ a ]pyrene (BaP) for AhR, dihydrotestosterone (DHT) for AR, dexamethasone (Dexa) for GR, and 17β-estradiol (E2) for ER. In this study, the H4IIE- luc bioassay with a shorter exposure time (4 h) was mainly focused on polar fractions, and thus, BaP was used as a reference material . Potency-based E2-equivalent concentrations (EQs) (ng E2-EQ L –1 ) were calculated from the dose–response curve for six concentrations.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, the H4IIE-luc bioassay with a shorter exposure time (4 h) was mainly focused on polar fractions, and thus, BaP was used as a reference material. 32 Potency-based E2-equivalent concentrations (EQs) (ng E2-EQ L −1 ) were calculated from the dose− response curve for six concentrations. All bioassays were conducted in triplicate to check reproducibility.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening

Gwak

Lee

Cha

et al. 2022

Environ. Sci. Technol.

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Endocrine-disrupting potential was evaluated during the sewage treatment process using in vitro bioassays. Aryl hydrocarbon receptor (AhR)-, androgen receptor (AR)-, glucocorticoid receptor (GR)-, and estrogen receptor (ER)-mediated activities were assessed over five steps of the treatment process. Bioassays of organic extracts showed that AhR, AR, and GR potencies tended to decrease through the sewage treatment process, whereas ER potencies did not significantly decrease. Bioassays on reverse-phase high-performance liquid chromatography fractions showed that F5 (log K OW 2.5–3.0) had great ER potencies. Full-scan screening of these fractions detected two novel ER agonists, arenobufagin and loratadine, which are used pharmaceuticals. These compounds accounted for 3.3–25% of the total ER potencies and 4% of the ER potencies in the final effluent. The well-known ER agonists, estrone and 17β-estradiol, accounted for 60 and 17% of the ER potencies in F5 of the influent and primary treatment, respectively. Fourier transform ion cyclotron resonance mass spectrometry analysis showed that various molecules were generated during the treatment process, especially CHO and CHOS (C: carbon, H: hydrogen, O: oxygen, and S: sulfur). This study documented that widely used pharmaceuticals are introduced into the aquatic environments without being removed during the sewage treatment process.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening

Gwak

Lee

Cha

et al. 2022

Environ. Sci. Technol.

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“…The typical xenobiotic AhR ligands include apolar planar organic compounds, such as halogenated aromatic hydrocarbons (HAHs), including dioxins, furans, and non-ortho-substituted polychlorinated biphenyls (PCBs), as well as a range of polyaromatic hydrocarbons (PAHs) [43,49]. Beyond these groups, certain polar organic compounds can also act as AhR ligands (e.g., [50]). Dioxins and related compounds enter the environment, for instance, as combustion products, as by-products in herbicides or wood preservatives, or from the bleaching process of Kraft pulp mills.…”

Section: Historical Foundationmentioning

confidence: 99%

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

Segner

Bailey²,

Tafalla³

et al. 2021

IJMS

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The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

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“…In addition, recent studies have identified novel polar AhR ligands that accumulate in aquatic environments. 4,5,7,8 Polar compounds are known to have increased bioavailability as they bind to membrane transport proteins and are transported into cells. 5 Effect-directed analysis (EDA) is a tool that combines the use of fractionations based on physicochemical properties with bioassays and instrumental analysis to identify bioactive constituents in environmental samples.…”

Section: ■ Introductionmentioning

confidence: 99%

Identification of Mid-Polar and Polar AhR Agonists in Cetaceans from Korean Coastal Waters: Application of Effect-Directed Analysis with Full-Scan Screening

Cha,

Hong,

Lee

et al. 2023

Environ. Sci. Technol.

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Major aryl hydrocarbon receptor (AhR) agonists were identified in extracts of blubber, liver, and muscle from six long-beaked common dolphins (Delphinus capensis) and one fin whale (Balaenoptera physalus) collected from Korean coastal waters using effect-directed analysis. Results of the H4IIE-luc bioassay indicated that the polar fractions of blubber and liver extracts from the fin whale exhibited relatively high AhR-mediated potencies. Based on full-scan screening with high-resolution mass spectrometry, 37 AhR agonist candidates, spanning four use categories: pharmaceuticals, pesticides, cosmetics, and natural products, were selected. Among these, five polar AhR agonists were newly identified through toxicological confirmation. Concentrations of polar AhR agonists in cetaceans were tissue-specific, with extracts of blubber and liver containing greater concentrations than muscle extracts. Polar AhR agonists with great log K OA values (>5) were found to biomagnify in the marine food chain potentially. Polar AhR agonists contributed 8.9% of the observed AhR-mediated potencies in blubber and 49% in liver. Rutaecarpine and alantolactone contributed significantly to the total AhR-mediated potencies of blubber, whereas hydrocortisone was a major AhR contributor in the liver of the fin whale. This study is the first to identify the tissue-specific accumulation of polar AhR agonists in blubber and liver extracts of cetaceans.

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Novel polar AhR-active chemicals detected in sediments of an industrial area using effect-directed analysis based on in vitro bioassays with full-scan high resolution mass spectrometric screening

Cited by 19 publications

References 86 publications

Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening

Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

Identification of Mid-Polar and Polar AhR Agonists in Cetaceans from Korean Coastal Waters: Application of Effect-Directed Analysis with Full-Scan Screening

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