title: Genome-wide differential gene expression in children exposed to air pollution in the Czech Republic.
abstract: The Teplice area in the Czech Republic is a mining district where elevated levels of air pollution including airborne carcinogens, have been demonstrated, especially during winter time. This environmental exposure can impact human health; in particular children may be more vulnerable. To study the impact of air pollution in children at the transcriptional level, peripheral blood cells were subjected to whole genome response analysis, in order to identify significantly modulated biological pathways and processes as a result of exposure. Using genome-wide oligonucleotide microarrays, we investigated differential gene expression in children from the Teplice area (n=23) and compared them with children from the rural control area of Prachatice (n=24). In an additional approach, individual gene expressions were correlated with individual peripheral blood lymphocyte micronuclei frequencies, in order to evaluate the linkage of individual gene expressions with an established biomarker of effect that is representative for increased genotoxic risk. Children from the Teplice area showed a significantly higher average micronuclei frequency than Prachatice children (p=0.023). For considerable numbers of genes, the expression differed significantly between the children from the two areas. Amongst these genes, considerable numbers of genes were observed to correlate significantly with the frequencies of micronuclei. The main biological process that appeared significantly affected overall was nucleosome assembly. This suggests an effect of air pollution on the primary structural unit of the condensed DNA. In addition, several other pathways were modulated. Based on the results of this study, we suggest that transcriptomic analysis represents a promising biomarker for environmental carcinogenesis.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: van Leeuwen
authors.forename: M H M
authors.initials: MH
authors.lastname: van Herwijnen
authors.forename: M
authors.initials: M
authors.lastname: Pedersen
authors.forename: L E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: M
authors.initials: M
authors.lastname: Kirsch-Volders
authors.forename: R J
authors.initials: RJ
authors.lastname: Sram
authors.forename: Y C M
authors.initials: YC
authors.lastname: Staal
authors.forename: E
authors.initials: E
authors.lastname: Bajak
authors.forename: J H M
authors.initials: JH
authors.lastname: van Delft
authors.forename: J C S
authors.initials: JC
authors.lastname: Kleinjans
mesh_terms: D000393:Air Pollutants; D000397:Air Pollution; D002648:Child; D018153:Czech Republic; D004781:Environmental Exposure; D005260:Female; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D000393:Air Pollutants