Maintenance of genome integrity in mammalian cells may be compromised by the concomitant accumulation of DNA damage and loss of repair functions. Polycyclic aromatic hydrocarbons are classic DNA-damaging and tumor-promoting agents. Benzo[a]pyrene (B[a]P), a prototype PAH, induces several genotoxic responses, including cell cycle arrest, oxidative stress and DNA adduct formation. Exposure of MCF-7 cells to B[a]P (1–5 μM) and the B[a]P diol epoxide (BPDE) (50–100 nM) induced transient S-phase arrest, which was followed by accumulation in G2 and M and 70% loss of cell viability. In cells treated with B[a]P and BPDE, we observed segregation of nucleolar material and a drastic reduction in the number of ribosomal fibrillar centers. To identify the expression profile in cells treated with B[a]P or BPDE, we analyzed the levels of expression of 1,152 selected genes using a GeneMAP CancerArray in control and treated cells. Changes in gene expression were evaluated twice in duplicate (n=4). Compared with the expression levels in untreated cells, transcripts that were upregulated by both B[a]P and BPDE included members of the cytochrome P450, AP-1 (Fra-1, Fra-2) and glutathione S-transferase families; PARP; and G1/S-specific cyclins. In contrast, transcript levels for BRCA-1, G2/M cyclins, bcl-2, junB and fosB were downregulated in cells treated with B[a]P or BPDE. Treatment with the metabolite BPDE tended to elicit a stronger response than treatment with B[a]P. Analysis of expression profiles by microarray may be useful to understand the interactions among overlapping pathways and assess exposure to environmental carcinogens.
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Romagnolo, D., Jeffy, B., Samuelson, D. et al. Microarray expression profiles in breast cancer MCF-7 cells following exposure to benzo[a]pyrene and its diol epoxide. Nat Genet 27 (Suppl 4), 83 (2001). https://doi.org/10.1038/87272
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DOI: https://doi.org/10.1038/87272