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Elucidation of xenoestrogen metabolism by non-targeted, stable isotope-assisted mass spectrometry in breast cancer cells
https://orcid.org/0000-0002-3518-3885
https://orcid.org/0000-0001-6568-2944
https://orcid.org/0000-0002-6104-0706
Graphical abstract Display Omitted
Highlights The mycoestrogen zearalenone was significantly metabolized by phase I biotransformation in MCF-7 cells to more estrogenic products. Glucuronidation and sulfation were prominent phase II reactions of both, zearalenone and genistein. Stable isotope-assisted metabolomics elucidated a novel, unexpected conjugation product of zearalenone with vitamin B6. Biotransformation of naturally occurring estrogenic compounds in cell models heavily impacts estrogenic potency.
Abstract Environmental exposure to xenoestrogens, i.e., chemicals that imitate the hormone 17β-estradiol, has the potential to influence hormone homeostasis and action. Detailed knowledge of xenobiotic biotransformation processes in cell models is key when transferring knowledge learned from in vitro models to in vivo relevance. This study elucidated the metabolism of two naturally-occurring phyto- and mycoestrogens; namely genistein and zearalenone, in an estrogen receptor positive breast cancer cell line (MCF-7) with the aid of stable isotope-assisted metabolomics and the bioinformatic tool MetExtract II. Metabolism was studied in a time course experiment after 2 h, 6 h and 24 h incubation. Twelve and six biotransformation products of zearalenone and genistein were detected, respectively, clearly demonstrating the abundant xenobiotic biotransformation capability of the cells. Zearalenone underwent extensive phase-I metabolism resulting in α-zearalenol (α-ZEL), a molecule known to possess a significantly higher estrogenicity, and several phase-II metabolites (sulfo- and glycoconjugates) of the native compound and the major phase I metabolite α-ZEL. Moreover, potential adducts of zearalenone with a vitamin and several hydroxylated metabolites were annotated. Genistein metabolism resulted in sulfation, combined sulfation and hydroxylation, acetylation, glucuronidation and unexpectedly adduct formation with pentose- and hexose sugars. Kinetics of metabolite formation and subsequent excretion into the extracellular medium revealed a time-dependent increase in most biotransformation products. The untargeted elucidation of biotransformation products formed during cell culture experiments enables an improved and more meaningful interpretation of toxicological assays and has the potential to identify unexpected or unknown metabolites.
Elucidation of xenoestrogen metabolism by non-targeted, stable isotope-assisted mass spectrometry in breast cancer cells
https://orcid.org/0000-0002-3518-3885
https://orcid.org/0000-0001-6568-2944
https://orcid.org/0000-0002-6104-0706
Graphical abstract Display Omitted
Highlights The mycoestrogen zearalenone was significantly metabolized by phase I biotransformation in MCF-7 cells to more estrogenic products. Glucuronidation and sulfation were prominent phase II reactions of both, zearalenone and genistein. Stable isotope-assisted metabolomics elucidated a novel, unexpected conjugation product of zearalenone with vitamin B6. Biotransformation of naturally occurring estrogenic compounds in cell models heavily impacts estrogenic potency.
Abstract Environmental exposure to xenoestrogens, i.e., chemicals that imitate the hormone 17β-estradiol, has the potential to influence hormone homeostasis and action. Detailed knowledge of xenobiotic biotransformation processes in cell models is key when transferring knowledge learned from in vitro models to in vivo relevance. This study elucidated the metabolism of two naturally-occurring phyto- and mycoestrogens; namely genistein and zearalenone, in an estrogen receptor positive breast cancer cell line (MCF-7) with the aid of stable isotope-assisted metabolomics and the bioinformatic tool MetExtract II. Metabolism was studied in a time course experiment after 2 h, 6 h and 24 h incubation. Twelve and six biotransformation products of zearalenone and genistein were detected, respectively, clearly demonstrating the abundant xenobiotic biotransformation capability of the cells. Zearalenone underwent extensive phase-I metabolism resulting in α-zearalenol (α-ZEL), a molecule known to possess a significantly higher estrogenicity, and several phase-II metabolites (sulfo- and glycoconjugates) of the native compound and the major phase I metabolite α-ZEL. Moreover, potential adducts of zearalenone with a vitamin and several hydroxylated metabolites were annotated. Genistein metabolism resulted in sulfation, combined sulfation and hydroxylation, acetylation, glucuronidation and unexpectedly adduct formation with pentose- and hexose sugars. Kinetics of metabolite formation and subsequent excretion into the extracellular medium revealed a time-dependent increase in most biotransformation products. The untargeted elucidation of biotransformation products formed during cell culture experiments enables an improved and more meaningful interpretation of toxicological assays and has the potential to identify unexpected or unknown metabolites.
Elucidation of xenoestrogen metabolism by non-targeted, stable isotope-assisted mass spectrometry in breast cancer cells
https://orcid.org/0000-0002-3518-3885
https://orcid.org/0000-0001-6568-2944
https://orcid.org/0000-0002-6104-0706
Graphical abstract Display Omitted
Highlights The mycoestrogen zearalenone was significantly metabolized by phase I biotransformation in MCF-7 cells to more estrogenic products. Glucuronidation and sulfation were prominent phase II reactions of both, zearalenone and genistein. Stable isotope-assisted metabolomics elucidated a novel, unexpected conjugation product of zearalenone with vitamin B6. Biotransformation of naturally occurring estrogenic compounds in cell models heavily impacts estrogenic potency.
Abstract Environmental exposure to xenoestrogens, i.e., chemicals that imitate the hormone 17β-estradiol, has the potential to influence hormone homeostasis and action. Detailed knowledge of xenobiotic biotransformation processes in cell models is key when transferring knowledge learned from in vitro models to in vivo relevance. This study elucidated the metabolism of two naturally-occurring phyto- and mycoestrogens; namely genistein and zearalenone, in an estrogen receptor positive breast cancer cell line (MCF-7) with the aid of stable isotope-assisted metabolomics and the bioinformatic tool MetExtract II. Metabolism was studied in a time course experiment after 2 h, 6 h and 24 h incubation. Twelve and six biotransformation products of zearalenone and genistein were detected, respectively, clearly demonstrating the abundant xenobiotic biotransformation capability of the cells. Zearalenone underwent extensive phase-I metabolism resulting in α-zearalenol (α-ZEL), a molecule known to possess a significantly higher estrogenicity, and several phase-II metabolites (sulfo- and glycoconjugates) of the native compound and the major phase I metabolite α-ZEL. Moreover, potential adducts of zearalenone with a vitamin and several hydroxylated metabolites were annotated. Genistein metabolism resulted in sulfation, combined sulfation and hydroxylation, acetylation, glucuronidation and unexpectedly adduct formation with pentose- and hexose sugars. Kinetics of metabolite formation and subsequent excretion into the extracellular medium revealed a time-dependent increase in most biotransformation products. The untargeted elucidation of biotransformation products formed during cell culture experiments enables an improved and more meaningful interpretation of toxicological assays and has the potential to identify unexpected or unknown metabolites.
Elucidation of xenoestrogen metabolism by non-targeted, stable isotope-assisted mass spectrometry in breast cancer cells
Flasch, Mira (Autor:in) / Bueschl, Christoph (Autor:in) / Del Favero, Giorgia (Autor:in) / Adam, Gerhard (Autor:in) / Schuhmacher, Rainer (Autor:in) / Marko, Doris (Autor:in) / Warth, Benedikt (Autor:in)
12.10.2021
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
| Elsevier | 2022
| British Library Online Contents | 2006
Male specific association between xenoestrogen levels in placenta and birthweight
| Online Contents | 2013