The Role of Metabolism in Toxicity of Polycyclic Aromatic Hydrocarbons and their Non-genotoxic Modes of Action

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00555644" target="_blank" >RIV/68081707:_____/21:00555644 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00027162:_____/21:N0000162

Výsledek na webu

<a href="https://www.eurekaselect.com/article/111851" target="_blank" >https://www.eurekaselect.com/article/111851</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1389200221999201125205725" target="_blank" >10.2174/1389200221999201125205725</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Role of Metabolism in Toxicity of Polycyclic Aromatic Hydrocarbons and their Non-genotoxic Modes of Action

Popis výsledku v původním jazyce

Polycyclic aromatic hydrocarbons (PAHs) represent a class of widely distributed environmental pollutants that have been primarily studied as genotoxic compounds. Their mutagenicity/genotoxicity largely depends on their oxidative metabolism leading to the production of dihydrodiol epoxide metabolites, as well as additional metabolites contributing to oxidative DNA damage, such as PAH quinones. However, both parental PAHs and their metabolites, including PAH quinones or hydroxylated PAHs, have been shown to produce various types of non-genotoxic effects. These include e.g., activation of the aryl hydrocarbon receptor and/or additional nuclear receptors, activation of membrane receptors, including tyrosine kinases and G-protein coupled receptors, or activation of intracellular signaling pathways, such as mitogen-activated protein kinases, Akt kinase and Ca2+-dependent signaling. These pathways may, together with the cellular DNA damage responses, modulate cell proliferation, cell survival or cell-to-cell communication, thus contributing to the known carcinogenic effects of PAHs. In the present review, we summarize some of the known non-genotoxic effects of PAHs, focusing primarily on those that have also been shown to be modulated by PAH metabolites. Despite the limitations of the available data, it seems evident that more attention should be paid to the discrimination between the potential non-genotoxic effects of parental PAHs and those of their metabolites. This may provide further insight into the mechanisms of toxicity of this large and diverse group of environmental pollutants.

Název v anglickém jazyce

The Role of Metabolism in Toxicity of Polycyclic Aromatic Hydrocarbons and their Non-genotoxic Modes of Action

Popis výsledku anglicky

Polycyclic aromatic hydrocarbons (PAHs) represent a class of widely distributed environmental pollutants that have been primarily studied as genotoxic compounds. Their mutagenicity/genotoxicity largely depends on their oxidative metabolism leading to the production of dihydrodiol epoxide metabolites, as well as additional metabolites contributing to oxidative DNA damage, such as PAH quinones. However, both parental PAHs and their metabolites, including PAH quinones or hydroxylated PAHs, have been shown to produce various types of non-genotoxic effects. These include e.g., activation of the aryl hydrocarbon receptor and/or additional nuclear receptors, activation of membrane receptors, including tyrosine kinases and G-protein coupled receptors, or activation of intracellular signaling pathways, such as mitogen-activated protein kinases, Akt kinase and Ca2+-dependent signaling. These pathways may, together with the cellular DNA damage responses, modulate cell proliferation, cell survival or cell-to-cell communication, thus contributing to the known carcinogenic effects of PAHs. In the present review, we summarize some of the known non-genotoxic effects of PAHs, focusing primarily on those that have also been shown to be modulated by PAH metabolites. Despite the limitations of the available data, it seems evident that more attention should be paid to the discrimination between the potential non-genotoxic effects of parental PAHs and those of their metabolites. This may provide further insight into the mechanisms of toxicity of this large and diverse group of environmental pollutants.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA18-00145S" target="_blank" >GA18-00145S: Pokročilé in vitro modely plicních epiteliálních buněk pro analýzu látek znečišťujících ovzduší</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Current Drug Metabolism

ISSN

1389-2002

e-ISSN

1875-5453

Svazek periodika

22

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

12

Strana od-do

584-595

Kód UT WoS článku

000725569000002

EID výsledku v databázi Scopus

2-s2.0-85118315273