Altered gene expression patterns in MCF-7 cells induced by the urban dust complex mixture SRM 1649 monitored using DNA microarrays.
Mahadevan-B; Keshava-C; Musafia-T; Pecaj-A; Weston-A; Baird-WM
Environ Mutagen 2003 Jan; 41(3):188
Human exposures to polycyclic aromatic hydrocarbons (PAHs) occur in complex mixtures In this study, gene expression patterns were investigated in MCF-7 cells exposed for 24h to Standard Reference Material (SRM) SRM 1649 alone or SRM 1649 plus either benzo[a]pyrene (BP) or dibenzo[a,l]pyrene (DBP) Gene expression was monitored using high density oligonucleotide arrays (Affymetrix U133A) representing more than 22,000 human genes and expressed sequence tags Duplicate treatments displayed a high degree of reproducibility Global analyses of the gene expression data revealed alterations of at least 2 fold change [signal log ratio (SLR) $ -1 or ~ 1] in 120 RNA transcripts in response to SRM 1649 exposure Increase in expression of CYP1A1 and CYP1 B1 was observed in response to BP exposure (SLR of 6.5 and 28, respectively) An additive induction of CYP1A1 and CYP1B1 was observed with co-treatment of SRM 1649 and BP (SLR of 75 and 33, respectively) On the contrary, DBP alone did not show any change in expression of CYP1A1 and CYP1 B 1, however, co-treatment of SRM 1649 and DBP showed an increase in expression of CYP1A1 and CYP1B1 (SLR of 24 and 2, respectively) The effect of complex PAH mixtures on the metabolic activation of carcinogenic PAH by GYP enzymes were correlated with the results from gene expression studies GYP enzyme activity was very similar to SRM 1649 alone in comparison with the co-treatment of SRM 1649 and BP Thus, we conclude that the data not only provides a transcriptional signature for chemical carcinogen exposure but also suggests that a major factor in carcinogenic activity of PAH within complex mixtures is the ability of the complex mixture to promote or inhibit the activation of carcinogenic PAH by the induction of GYP metabolic enzymes
Polycyclic-aromatic-hydrocarbons; Genes; Genetic-factors; Benzopyrenes; Carcinogens; Carcinogenicity
Conference/Symposia Proceedings; Abstract
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease