van Leeuwen D M, van Herwijnen M H M, Pedersen M, Knudsen L E, Kirsch-Volders M, Sram R J, Staal Y C M, Bajak E, van Delft J H M, Kleinjans J C S
Department of Health Risk Analysis and Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Mutat Res. 2006 Aug 30;600(1-2):12-22. doi: 10.1016/j.mrfmmm.2006.05.032. Epub 2006 Jul 11.
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.
捷克共和国的特普利采地区是一个矿区,已证实该地区空气污染水平升高,包括空气中的致癌物,尤其是在冬季。这种环境暴露会影响人类健康;尤其是儿童可能更易受到影响。为了在转录水平上研究空气污染对儿童的影响,对外周血细胞进行了全基因组反应分析,以确定暴露后显著调节的生物学途径和过程。我们使用全基因组寡核苷酸微阵列,研究了特普利采地区儿童(n = 23)的基因表达差异,并将他们与普拉哈蒂采农村对照地区的儿童(n = 24)进行比较。在另一种方法中,将个体基因表达与个体外周血淋巴细胞微核频率相关联,以评估个体基因表达与代表遗传毒性风险增加的既定效应生物标志物之间的联系。特普利采地区的儿童平均微核频率显著高于普拉哈蒂采地区的儿童(p = 0.023)。对于相当数量的基因,两个地区儿童的表达存在显著差异。在这些基因中,观察到相当数量的基因与微核频率显著相关。总体上受显著影响的主要生物学过程是核小体组装。这表明空气污染对浓缩DNA的主要结构单元有影响。此外,其他几个途径也受到了调节。基于本研究结果,我们认为转录组分析是环境致癌作用的一种有前景的生物标志物。