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Statements

Subject Item
n2:RIV%2F00027162%3A_____%2F08%3A%230000452%21RIV09-MZE-00027162
rdf:type
skos:Concept n14:Vysledek
dcterms:description
Vzhledem k tomu, že chronický zánět přispívá ke karcinogenezi, studovali jsme interakci hlavního prozánětlivého cytokinu TNF-alfa a benzo[a]pyrenu (BaP) na indukci exprese CYP1A1/1B1 a poškození DNA. TNF-alfa zvyšoval indukci CYP1B1 a současně snižoval BaP-navozenou expresi CYP1A1. Tato deregulace CYP1 indukce měla souvislost se zvýšenou tvorbou DNA aduktů, která korespondovala se zvýšenou fosforylací tumorového supresora p53 na Ser15, s větším množstvím buněk v S-fázi buněčného cyklu a se zvýšením BaP-navozené apoptózy. As the chronic inflammation is known to contribute to carcinogenesis, we investigated interactions of a major proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and benzo[a]pyrene (BaP) in regulation of the expression of CYP1A1/1B1 and induction of DNA damage in rat liver epithelial WB-F344 cells. TNF-alpha enhanced induction of CYP1B1, while it simultaneously suppressed the BaP-induced CYP1A1 expression. The observed deregulation of CYP1 induction was found to be associated with a significantly enhanced formation of DNA adducts. The elevated DNA damage corresponded with increased phosphorylation of p53 tumor suppressor at Ser-15 residue, enhanced accumulation of cells in the S-phase of cell cycle and potentiation of BaP-induced apoptosis. Our results seem to indicate that inflammatory conditions might enhance genotoxic effects of carcinogenic polycyclic aromatic hydrocarbons through upregulation of CYP1B1 expression. As the chronic inflammation is known to contribute to carcinogenesis, we investigated interactions of a major proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and benzo[a]pyrene (BaP) in regulation of the expression of CYP1A1/1B1 and induction of DNA damage in rat liver epithelial WB-F344 cells. TNF-alpha enhanced induction of CYP1B1, while it simultaneously suppressed the BaP-induced CYP1A1 expression. The observed deregulation of CYP1 induction was found to be associated with a significantly enhanced formation of DNA adducts. The elevated DNA damage corresponded with increased phosphorylation of p53 tumor suppressor at Ser-15 residue, enhanced accumulation of cells in the S-phase of cell cycle and potentiation of BaP-induced apoptosis. Our results seem to indicate that inflammatory conditions might enhance genotoxic effects of carcinogenic polycyclic aromatic hydrocarbons through upregulation of CYP1B1 expression.
dcterms:title
Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in rat liver epithelial cells through upregulation of cytochrome P450 1B1 expression Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in rat liver epithelial cells through upregulation of cytochrome P450 1B1 expression TNF-alfa zesiloval genotoxický účinek benzo[a]pyrenu v krysích jaterních epiteliálních buňkách pomocí zvýšené expresi cytochromu P4501B1
skos:prefLabel
Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in rat liver epithelial cells through upregulation of cytochrome P450 1B1 expression TNF-alfa zesiloval genotoxický účinek benzo[a]pyrenu v krysích jaterních epiteliálních buňkách pomocí zvýšené expresi cytochromu P4501B1 Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in rat liver epithelial cells through upregulation of cytochrome P450 1B1 expression
skos:notation
RIV/00027162:_____/08:#0000452!RIV09-MZE-00027162
n3:aktivita
n15:P n15:Z
n3:aktivity
P(GA524/05/0595), Z(AV0Z50040507), Z(AV0Z50040702), Z(AV0Z50390512), Z(AV0Z50390703), Z(MZE0002716201)
n3:cisloPeriodika
1-2
n3:dodaniDat
n6:2009
n3:domaciTvurceVysledku
n8:3547884 n8:5686350 n8:2301229
n3:druhVysledku
n13:J
n3:duvernostUdaju
n18:S
n3:entitaPredkladatele
n9:predkladatel
n3:idSjednocenehoVysledku
400812
n3:idVysledku
RIV/00027162:_____/08:#0000452
n3:jazykVysledku
n12:eng
n3:klicovaSlova
TNF-alpha; BaP; CYP1B1; liver progenitor cells; AhR; DNA adducts
n3:klicoveSlovo
n10:DNA%20adducts n10:TNF-alpha n10:AhR n10:BaP n10:CYP1B1 n10:liver%20progenitor%20cells
n3:kodStatuVydavatele
NL - Nizozemsko
n3:kontrolniKodProRIV
[79C14106DF29]
n3:nazevZdroje
Mutat Res.- Fundam. Mol. Mechan. Mutagen.
n3:obor
n17:DN
n3:pocetDomacichTvurcuVysledku
3
n3:pocetTvurcuVysledku
7
n3:projekt
n4:GA524%2F05%2F0595
n3:rokUplatneniVysledku
n6:2008
n3:svazekPeriodika
640
n3:tvurceVysledku
Machala, Miroslav Nováková, Z. Kozubík, A. Vondráček, Jan Umannová, Lenka Topinka, J. Milcová, A.
n3:wos
000255080700019
n3:zamer
n5:AV0Z50390703 n5:AV0Z50390512 n5:AV0Z50040702 n5:AV0Z50040507 n5:MZE0002716201
s:issn
0027-5107
s:numberOfPages
8