Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F10%3A%230000687" target="_blank" >RIV/00027162:_____/10:#0000687 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/10:00347299 RIV/68378041:_____/10:00347299

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells

Popis výsledku v původním jazyce

Exposure to polycyclic aromatic hydrocarbons has been positively associated with prostate cancer, but knowledge of the formation of PAH-DNA adducts and related genotoxic events in prostatic cells is limited. In the present study, benzo[a]pyrene, formed significant levels of DNA adducts in cell lines derived from human prostate carcinoma. Despite a significant amount of DNA adducts being formed, neither apoptosis nor cell-cycle arrest were induced in LNCaP cells, presumably due to their failure to activate the p53-dependent DNA damage response. LNCaP cells were not sensitized to the induction of apoptosis by PAHs even through inhibition of the PI3K/Akt pro-survival pathway and the lack of apoptosis was not due a disruption of expression of pro-apoptoticand pro-survival members of the Bcl-2 family of apoptosis regulators. In contrast to other genotoxic stimuli, genotoxic PAHs failed to induce DNA double-strand breaks, as illustrated by the lack of phosphorylation of histone H2AX or Chk-

Název v anglickém jazyce

Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells

Popis výsledku anglicky

Exposure to polycyclic aromatic hydrocarbons has been positively associated with prostate cancer, but knowledge of the formation of PAH-DNA adducts and related genotoxic events in prostatic cells is limited. In the present study, benzo[a]pyrene, formed significant levels of DNA adducts in cell lines derived from human prostate carcinoma. Despite a significant amount of DNA adducts being formed, neither apoptosis nor cell-cycle arrest were induced in LNCaP cells, presumably due to their failure to activate the p53-dependent DNA damage response. LNCaP cells were not sensitized to the induction of apoptosis by PAHs even through inhibition of the PI3K/Akt pro-survival pathway and the lack of apoptosis was not due a disruption of expression of pro-apoptoticand pro-survival members of the Bcl-2 family of apoptosis regulators. In contrast to other genotoxic stimuli, genotoxic PAHs failed to induce DNA double-strand breaks, as illustrated by the lack of phosphorylation of histone H2AX or Chk-

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

DN - Vliv životního prostředí na zdraví

OECD FORD obor

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Projekt

<a href="/cs/project/GA310%2F07%2F0961" target="_blank" >GA310/07/0961: Úloha environmentálních polutantů v mechanismech regulujících vznik a vývoj karcinomu prostaty</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

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

Název periodika

TOXICOLOGY LETTERS

ISSN

0378-4274

e-ISSN

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Svazek periodika

197

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

9

Strana od-do

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Kód UT WoS článku

000281002700011

EID výsledku v databázi Scopus

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