Altered Gene Expression Patterns in MCF-7 Cells Induced by the Urban Dust Particulate Complex Mixture Standard Reference Material 1649a

Abstract

Human exposures to polycyclic aromatic hydrocarbon (PAH) occur in complex mixtures. Here, gene expression patterns were investigated using standard reference material (SRM) 1649a (urban dust). MCF-7 cells were exposed to SRM 1649a alone or SRM 1649a with either benzo[a]pyrene (BP) or dibenzo [a,l]pyrene (DBP) for 24 hours. Global analyses of the gene expression data revealed alterations of 41 RNA transcripts with at least 2-fold change (signal log ratio V À1 or z 1) in response to SRM 1649a exposure. Increase in expression of cytochrome P450 (CYP) genes was observed in response to BP exposure (CYP1A1 and CYP1B1; signal log ratio of 4.7 and 2.5, respectively). An additive induction of CYP1A1 and CYP1B1 was observed with cotreatment of SRM 1649a and BP. On the contrary, no change in gene expression of CYP1A1 and CYP1B1 was observed when the cells were exposed to DBP. Furthermore, to study the effect of complex PAH mixtures on the metabolic activation of carcinogenic PAH to DNA-binding derivatives and to relate this with gene expression studies, PAH-DNA adduct formation was determined. SRM 1649a decreased the total level of BP-DNA adducts in comparison with BP alone. No significant difference in adduct levels was observed in response to either DBP alone or in combination with SRM 1649a. These results provide a transcriptional signature for chemical carcinogen exposure; in addition, they suggest a major factor in carcinogenic activity of PAH within complex mixtures is their ability to promote or inhibit the activation of carcinogenic PAH by the induction of CYP enzymes. (Cancer Res 2005; 65(4): 1251-8)

Genome-wide H3K9 Histone Acetylation Profiles Are Altered in Benzopyrene-treated MCF7 Breast Cancer Cells

“…A previous report described how in vitro exposure of MCF7 cells to BaP led to expression changes in genes involved in a variety of cell functions and pathways (16). We identified striking similarities between our data and the gene list reported by this group (Table 2).…”

“…For example, dietary fluctuations, such as low folate levels, can alter methyl metabolism, shift methylation patterns, and change gene expression (13,14). Similarly, exposures to environmental pollutants such as vehicular exhaust, tobacco smoke, and heavy metals elicit epigenetic changes and affect genes involved in DNA repair, apoptosis, or chemical detoxification pathways (15,16).…”

The influence of diesel exhaust on polycyclic aromatic hydrocarbon-induced DNA damage, gene expression, and tumor initiation in Sencar mice in vivo

“…Although PAHs are typically found in complex mixtures, much of the PAH research has focused on the effects of individual, potent carcinogenic member compounds such as BP or DBP. Due to difficulties and uncertainties in scientific evaluation, limited research has been done on binary or artificial mixtures [19][20][21][22][23][24], and to a lesser extent on complex mixtures [25][26][27]. These previous studies have focused primarily on the genotoxic effects of PAHs (e.g.…”

Exposure to Nano-Sized Particles and the Emergence of Contemporary Diseases with a Focus on Epigenetics

“…(Bacarelli 2009;Nawrot & Adcock, 2009) It soon became evident that the persistent effects of air pollution have a more pronounced effect on the phenotype rather than on the genotype. (Yauk et al, 2007;Vineis & Husgafvel-Pursiainen, 2005;Mahadevan et al, 2005) These findings support the already pursued hypothesis that mutagenic volatile chemicals adsorbed onto airborne particle pollutants induce somatic and germ-line mutations. While it was not always apparent why and how these mutations do occur, recent evidence suggests that a sensitive, easy to modulate layer (via methylation, acetylation, phosphorylation, etc.)…”