%0 Journal Article
%T Global gene expression changes in human embryonic lung fibroblasts induced by organic extracts from respirable air particles
%A Helena L¨ªbalov¨¢
%A Kate£¿ina Uhl¨ª£¿ov¨¢
%A Ji£¿¨ª Kl¨¦ma
%A Miroslav Machala
%A Radim J £¿r¨¢m
%A Miroslav Ciganek
%A Jan Topinka
%J Particle and Fibre Toxicology
%D 2012
%I BioMed Central
%R 10.1186/1743-8977-9-1
%X For this purpose, HEL cells were incubated with subtoxic EOM concentrations of 10, 30, and 60 ¦Ìg EOM/ml for 24 hours and global gene expression changes were analyzed using human whole genome microarrays (Illumina). The expression of selected genes was verified by quantitative real-time PCR.Dose-dependent increases in the number of significantly deregulated transcripts as well as dose-response relationships in the levels of individual transcripts were observed. The transcriptomic data did not differ substantially between the localities, suggesting that the air pollution originating mainly from various sources may have similar biological effects. This was further confirmed by the analysis of deregulated pathways and by identification of the most contributing gene modulations. The number of significantly deregulated KEGG pathways, as identified by Goeman's global test, varied, depending on the locality, between 12 to 29. The Metabolism of xenobiotics by cytochrome P450 exhibited the strongest upregulation in all 4 localities and CYP1B1 had a major contribution to the upregulation of this pathway. Other important deregulated pathways in all 4 localities were ABC transporters (involved in the translocation of exogenous and endogenous metabolites across membranes and DNA repair), the Wnt and TGF-¦Â signaling pathways (associated particularly with tumor promotion and progression), Steroid hormone biosynthesis (involved in the endocrine-disrupting activity of chemicals), and Glycerolipid metabolism (pathways involving the lipids with a glycerol backbone including lipid signaling molecules).The microarray data suggested a prominent role of activation of aryl hydrocarbon receptor-dependent gene expression.Considerable efforts have been made to clarify the adverse effects of environmental pollution on human health [1]. Respirable ambient air particulate matter with an aerodynamic diameter < 2.5 ¦Ìm (PM2.5) is a complex mixture consisting of a large number of chemicals, many of w
%K air pollution
%K complex mixtures
%K HEL cells
%K CYP1B1
%K AhR
%K gene expression profile
%U http://www.particleandfibretoxicology.com/content/9/1/1