Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53.

2.50
Hdl Handle:
http://hdl.handle.net/10146/36713
Title:
Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53.
Authors:
Hockley, Sarah L.; Arlt, Volker M.; Jahnke, Gunnar; Hartwig, Andrea; Giddings, Ian; Phillips, David H.
Abstract:
Human colon carcinoma cells (HCT116) differing in p53 status were exposed to benzo(a)pyrene (BaP) or anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) and their gene expression responses compared by complementary DNA microarray technology. Exposure of cells to BPDE for up to 24 h resulted in gene expression profiles more distinguishable by duration of exposure than by p53 status, although a subset of genes were identified that had significantly different expression in p53 wild-type (WT) cells relative to p53-null cells. Apoptotic signalling genes were up-regulated in p53-WT cells but not in p53-null cells and, consistent with this, reduced viability and caspase activity were also p53 dependent. BPDE modulated cell cycle and histone genes in both cell lines and, in agreement with this, both cell lines accumulated in S phase. In p53-WT cells, G(2) arrest was also evident, which was associated with accumulation of CDKN1A. Regardless of p53 status, exposure to BaP for up to 48 h had subtle effects on gene transcription and had no influence on cell viability or cell cycle. Interestingly, DNA adduct formation after BaP, but not BPDE, exposure was p53 dependent with 10-fold lower levels detected in p53-null cells. Other cell lines were investigated for BaP-DNA adduct formation and in these the effect of p53 knockdown was also to reduce adduct formation. Taken together, these results give further insight into the role of p53 in the response of human cells to BaP and BPDE and suggest that loss of this tumour suppressor can influence the metabolic activation of BaP.
Citation:
Carcinogenesis 2008, 29 (1):202-210
Journal:
Carcinogenesis
Issue Date:
Jan-2008
URI:
http://hdl.handle.net/10146/36713
DOI:
10.1093/carcin/bgm227
PubMed ID:
17942461
Additional Links:
http://carcin.oxfordjournals.org/cgi/content/full/29/1/202
Type:
Article
Language:
en
ISSN:
1460-2180
Sponsors:
The authors (S.L.H., V.M.A. and D.H.P.) are partners of Environmental Cancer Risk, Nutrition and Individual Susceptibility, a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorHockley, Sarah L.-
dc.contributor.authorArlt, Volker M.-
dc.contributor.authorJahnke, Gunnar-
dc.contributor.authorHartwig, Andrea-
dc.contributor.authorGiddings, Ian-
dc.contributor.authorPhillips, David H.-
dc.date.accessioned2008-08-28T09:45:25Z-
dc.date.available2008-08-28T09:45:25Z-
dc.date.issued2008-01-
dc.identifier.citationCarcinogenesis 2008, 29 (1):202-210en
dc.identifier.issn1460-2180-
dc.identifier.pmid17942461-
dc.identifier.doi10.1093/carcin/bgm227-
dc.identifier.urihttp://hdl.handle.net/10146/36713-
dc.description.abstractHuman colon carcinoma cells (HCT116) differing in p53 status were exposed to benzo(a)pyrene (BaP) or anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) and their gene expression responses compared by complementary DNA microarray technology. Exposure of cells to BPDE for up to 24 h resulted in gene expression profiles more distinguishable by duration of exposure than by p53 status, although a subset of genes were identified that had significantly different expression in p53 wild-type (WT) cells relative to p53-null cells. Apoptotic signalling genes were up-regulated in p53-WT cells but not in p53-null cells and, consistent with this, reduced viability and caspase activity were also p53 dependent. BPDE modulated cell cycle and histone genes in both cell lines and, in agreement with this, both cell lines accumulated in S phase. In p53-WT cells, G(2) arrest was also evident, which was associated with accumulation of CDKN1A. Regardless of p53 status, exposure to BaP for up to 48 h had subtle effects on gene transcription and had no influence on cell viability or cell cycle. Interestingly, DNA adduct formation after BaP, but not BPDE, exposure was p53 dependent with 10-fold lower levels detected in p53-null cells. Other cell lines were investigated for BaP-DNA adduct formation and in these the effect of p53 knockdown was also to reduce adduct formation. Taken together, these results give further insight into the role of p53 in the response of human cells to BaP and BPDE and suggest that loss of this tumour suppressor can influence the metabolic activation of BaP.en
dc.description.sponsorshipThe authors (S.L.H., V.M.A. and D.H.P.) are partners of Environmental Cancer Risk, Nutrition and Individual Susceptibility, a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’.en
dc.language.isoenen
dc.relation.urlhttp://carcin.oxfordjournals.org/cgi/content/full/29/1/202en
dc.subject.mesh7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide-
dc.subject.meshApoptosis-
dc.subject.meshBenzo(a)pyrene-
dc.subject.meshCarcinogens-
dc.subject.meshCell Line, Tumor-
dc.subject.meshGene Expression Profiling-
dc.subject.meshHumans-
dc.subject.meshOligonucleotide Array Sequence Analysis-
dc.subject.meshTumor Suppressor Protein p53-
dc.titleIdentification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen
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