Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsHockley, Sarah L.
Arlt, Volker M.
Phillips, David H.
MetadataShow full item record
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.
CitationCarcinogenesis 2008, 29 (1):202-210
SponsorsThe 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’.
- Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2.
- Authors: Hockley SL, Arlt VM, Brewer D, Giddings I, Phillips DH
- Issue date: 2006 Oct 16
- Gene expression profiles and genetic damage in benzo(a)pyrene diol epoxide-exposed TK6 cells.
- Authors: Akerman GS, Rosenzweig BA, Domon OE, McGarrity LJ, Blankenship LR, Tsai CA, Culp SJ, MacGregor JT, Sistare FD, Chen JJ, Morris SM
- Issue date: 2004 May 18
- Enhanced sensitivity to anti-benzo(a)pyrene-diol-epoxide DNA damage correlates with decreased global genomic repair attributable to abrogated p53 function in human cells.
- Authors: Wani MA, Zhu Q, El-Mahdy M, Venkatachalam S, Wani AA
- Issue date: 2000 Apr 15
- Expression of human glutathione S-transferase P1 confers resistance to benzo[a]pyrene or benzo[a]pyrene-7,8-dihydrodiol mutagenesis, macromolecular alkylation and formation of stable N2-Gua-BPDE adducts in stably transfected V79MZ cells co-expressing hCYP1A1.
- Authors: Kushman ME, Kabler SL, Fleming MH, Ravoori S, Gupta RC, Doehmer J, Morrow CS, Townsend AJ
- Issue date: 2007 Jan
- Arsenite enhances the benzo[a]pyrene diol epoxide (BPDE)-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts in human lung cells.
- Authors: Chiang HC, Tsou TC
- Issue date: 2009 Aug