Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F18%3AN0000164" target="_blank" >RIV/00027162:_____/18:N0000164 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/18:00494990 RIV/00216224:14310/18:00106522

Result on the web

<a href="https://academic.oup.com/toxsci/article/165/2/447/5042910" target="_blank" >https://academic.oup.com/toxsci/article/165/2/447/5042910</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/toxsci/kfy153" target="_blank" >10.1093/toxsci/kfy153</a>

Result language

angličtina

Original language name

Aryl Hydrocarbon Receptor-Dependent Metabolism Plays a Significant Role in Estrogen-Like Effects of Polycyclic Aromatic Hydrocarbons on Cell Proliferation

Original language description

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that interact in a complex manner with both the aryl hydrocarbon receptor (AhR) and estrogen receptors (ER). Their potential endocrine-disrupting activities may depend on both inhibitory AhR-ER cross-talk and on AhR-dependent metabolic production of estrogenic PAH metabolites. Here, we analyzed the impact of AhR on estrogen-like effects of PAHs, such as benzo[a]pyrene (BaP), in particular, on control of cell cycle progression/cell proliferation. Using AhR knockout variant of estrogen-sensitive human breast cancer MCF-7 cells (MCF-7 AhRKO cells), we observed that the AhR-dependent control of cytochrome P450 family 1 (CYP1) expression played a major role in formation of estrogenic BaP metabolites, most notably 3-OH-BaP, which contributed to the ER-dependent induction of cell cycle progression/cell proliferation. Both BaP metabolism and the BaPinduced S-phase transition/cell proliferation were inhibited in MCF-7 AhRKO cells, whereas these cells remained sensitive towards both endogenous estrogen 17b-estradiol or hydroxylated BaP metabolites. BaP was found to increase the activity of ER-dependent luciferase reporter gene in wild-type MCF-7 cells; however, unlike its hydroxylated metabolite, BaP failed to stimulate luciferase activity in MCF-7 AhRKO cells. Similarly, estrogen-like effects of other known estrogenic PAHs, such as benz[a]anthracene or 3-methylcholanthrene, were diminished in MCF-7 AhRKO cells. Ectopic expression of human CYP1A1 and CYP1B1 enzymes partly restored both BaP metabolism and its effects on cell proliferation. Taken together, our data suggest that the AhR-dependent metabolismof PAHs contributes significantly to the impact of PAHs on cell proliferation in estrogen-sensitive cells.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

<a href="/en/project/GA16-17085S" target="_blank" >GA16-17085S: Dual action of environmental toxicants on the aryl hydrocarbon and estrogen receptors</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Toxicological Sciences

ISSN

1096-6080

e-ISSN

1096-0929

Volume of the periodical

165

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

447-461

UT code for WoS article

000446112900020

EID of the result in the Scopus database

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