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

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

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Description	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-apoptotic and 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-2 activation. 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-apoptotic and 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-2 activation. (en)
Title	Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells (en)
skos:prefLabel	Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells Genotoxic polycyclic aromatic hydrocarbons fail to induce the p53-dependent DNA damage response, apoptosis or cell-cycle arrest in human prostate carcinoma LNCaP cells (en)
skos:notation	RIV/00027162:_____/10:#0000687!RIV11-GA0-00027162
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(GA310/07/0961), Z(AV0Z50040507), Z(AV0Z50040702), Z(AV0Z50390512), Z(AV0Z50390703), Z(MZE0002716202)
http://linked.open...iv/cisloPeriodika	3
http://linked.open...vai/riv/dodaniDat	2011
http://linked.open...aciTvurceVysledku	Machala, Miroslav Vondráček, Jan Pálková, Lenka Krčmář, Pavel Hrubá, Eva Trilecová, Lenka Marvanová, Soňa
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Výzkumný ústav veterinárního lékařství, v.v.i.
http://linked.open...dnocenehoVysledku	260484
http://linked.open...ai/riv/idVysledku	RIV/00027162:_____/10:#0000687
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Prostate epithelial cells; DNA adducts; Apoptosis; Cell-cycle arrest; p53; Carcinogenesis (en)
http://linked.open.../riv/klicoveSlovo	Apoptosis DNA adducts p53 Carcinogenesis Cell-cycle arrest Prostate epithelial cells
http://linked.open...odStatuVydavatele	IE - Irsko
http://linked.open...ontrolniKodProRIV	[6C39710969EB]
http://linked.open...i/riv/nazevZdroje	TOXICOLOGY LETTERS
http://linked.open...in/vavai/riv/obor	DN
http://linked.open...ichTvurcuVysledku	7 (xsd:int)
http://linked.open...cetTvurcuVysledku	12 (xsd:int)
http://linked.open...vavai/riv/projekt	The role of environmental pollutants in mechanisms regulating development of prostate carcinoma
http://linked.open...UplatneniVysledku	2010
http://linked.open...v/svazekPeriodika	197
http://linked.open...iv/tvurceVysledku	Vondráček, Jan Machala, Miroslav Topinka, J. Hrubá, Eva Krčmář, Pavel Marvanová, Soňa Milcová, A. Trilecová, Lenka Vykopalová, Lenka Libalová, H. Souček, K. Starsichova, A.
http://linked.open...ain/vavai/riv/wos	000281002700011
http://linked.open...n/vavai/riv/zamer	Biophysics of dynamic structures and functions of biological systems Genome and epigenome: 1D and 3D Structure, Dynamics, Interactions with Proteins and Functions Molekulární, buněčné a systémové mechanizmy závažných onemocnění lidského organizmu, jejich diagnostika, terapie a farmakoterapie New biotechnologies, nanomaterials and stem cells for use in regenerative medicine Animal disease research, prevention and food chain protection
issn	0378-4274
number of pages	9 (xsd:int)

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