Neglegted polycyclic aromatic sulphur heterocycles: benzo[b]naphtho[d]thiophenes and naphthylbenzo[b]thiophenes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F23%3AN0000107" target="_blank" >RIV/00027162:_____/23:N0000107 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Neglegted polycyclic aromatic sulphur heterocycles: benzo[b]naphtho[d]thiophenes and naphthylbenzo[b]thiophenes

Popis výsledku v původním jazyce

Oral presentation. In: Genetická toxikológia a prevencia rakoviny, Smolenice, Slovensko, 12.-15.6.2023, p. 28. Polycyclic aromatic sulphur heterocycles (PASHs) belong among ubiquitous environmental pollutants. They originate from similar sources as polycyclic aromatic hydrocarbons (PAHs), and they usually accompany PAHs in the same samples; however, their toxic effects remain poorly understood. So far, IARC evaluated only two PASHs, dibenzothiophene (DBT) and benzo[b]naphtho[2,1-d]thiophene (BN21T), and categorized them in Group 3, as there is inadequate (for DBT), or limited (for BN21T) evidence for their carcinogenicity in experimental animals. Here, we studied the aryl hydrocarbon receptor (AhR)-mediated activities of DBT, benzo[b]naphtho[d]thiophenes (BNTs), and naphthylbenzo[b]thiophenes (NBTs), as well as their presence in two types of environmental matrices: river sediments collected from both rural and urban areas, and in airborne particulate matter (PM2.5) sampled in cities with different levels and sources of pollution. BN21T, BN23T, 22NBT, and 21NBT were newly identified as efficient AhR agonists in both rat and human AhR-based reporter gene assays, with 22NBT being the most potent compound identified in both species. BNTs were dominant PASHs present in both PM2.5 and sediment samples, with BN21T being the most abundant one, followed by BN23T. The levels of NBTs were mostly low or below detection limit. BN21T and BN23T were identified as the most significant contributors to the AhR-mediated activity in the environmental samples evaluated in this study. Both induced nuclear translocation of the AhR and CYP1A1 expression in a time-dependent manner. Independently of their ability to activate the AhR, BN12T, 21NBT, 31NBT, and 32NBT inhibited gap junctional intercellular communication in a model of rat liver epithelial cells. In conclusion, not only BN21T, but also other PASHs, such as BN23T should be studied more deeply, and included in risk assessment of relevant exposure scenarios. Importantly, effects of NBTs, although these PASHs do not appear to be ubiquitously distributed, should not be disregarded, as they can be present at significant levels in heavily polluted industrial locations. In particular, 22NBT that elicits very strong AhR-mediated activity should be further studied as potentially relevant environmental AhR-active contaminant. Alternative toxic modes of action, such as inhibition of GJIC could also be relevant for some PASHs, in particular NBTs. More attention should be paid to the potential health impacts of PASHs and their environmental distribution.

Název v anglickém jazyce

Neglegted polycyclic aromatic sulphur heterocycles: benzo[b]naphtho[d]thiophenes and naphthylbenzo[b]thiophenes

Popis výsledku anglicky

Oral presentation. In: Genetická toxikológia a prevencia rakoviny, Smolenice, Slovensko, 12.-15.6.2023, p. 28. Polycyclic aromatic sulphur heterocycles (PASHs) belong among ubiquitous environmental pollutants. They originate from similar sources as polycyclic aromatic hydrocarbons (PAHs), and they usually accompany PAHs in the same samples; however, their toxic effects remain poorly understood. So far, IARC evaluated only two PASHs, dibenzothiophene (DBT) and benzo[b]naphtho[2,1-d]thiophene (BN21T), and categorized them in Group 3, as there is inadequate (for DBT), or limited (for BN21T) evidence for their carcinogenicity in experimental animals. Here, we studied the aryl hydrocarbon receptor (AhR)-mediated activities of DBT, benzo[b]naphtho[d]thiophenes (BNTs), and naphthylbenzo[b]thiophenes (NBTs), as well as their presence in two types of environmental matrices: river sediments collected from both rural and urban areas, and in airborne particulate matter (PM2.5) sampled in cities with different levels and sources of pollution. BN21T, BN23T, 22NBT, and 21NBT were newly identified as efficient AhR agonists in both rat and human AhR-based reporter gene assays, with 22NBT being the most potent compound identified in both species. BNTs were dominant PASHs present in both PM2.5 and sediment samples, with BN21T being the most abundant one, followed by BN23T. The levels of NBTs were mostly low or below detection limit. BN21T and BN23T were identified as the most significant contributors to the AhR-mediated activity in the environmental samples evaluated in this study. Both induced nuclear translocation of the AhR and CYP1A1 expression in a time-dependent manner. Independently of their ability to activate the AhR, BN12T, 21NBT, 31NBT, and 32NBT inhibited gap junctional intercellular communication in a model of rat liver epithelial cells. In conclusion, not only BN21T, but also other PASHs, such as BN23T should be studied more deeply, and included in risk assessment of relevant exposure scenarios. Importantly, effects of NBTs, although these PASHs do not appear to be ubiquitously distributed, should not be disregarded, as they can be present at significant levels in heavily polluted industrial locations. In particular, 22NBT that elicits very strong AhR-mediated activity should be further studied as potentially relevant environmental AhR-active contaminant. Alternative toxic modes of action, such as inhibition of GJIC could also be relevant for some PASHs, in particular NBTs. More attention should be paid to the potential health impacts of PASHs and their environmental distribution.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GA21-00533S" target="_blank" >GA21-00533S: Nekonvenční environmentální ligandy Ah receptoru a jejich komplexní účinky in vitro</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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