Transcriptomic fingerprints in human peripheral blood mononuclear cells indicative of genotoxic and non-genotoxic carcinogenic exposure

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• 作者：K. Hochstenbach^a ; ^{Kevin.Hochstenbach@maastrichtuniversity.nl} ; D.M. van Leeuwen^a ; ^{D.vanLeeuwen@maastrichtuniversity.nl} ; R.W. Gottschalk^a ; ^{R.Gottschalk@mumc.nl} ; H. Gmuender^b ; ^{Hans.Gmuender@genedata.com} ; S.B. Stø ; levik^c ; ^{Solvor.Berntsen@fhi.no} ; U.C. Nygaard^c ; ^{Unni.Cecilie.Nygaard@fhi.no} ; M. Lø ; vik^c ; ^d ; ^{Martinus.Lovik@fhi.no} ; B. Granum^c ; ^{Berit.Granum@fhi.no} ; E. Namork^c ; ^{Ellen.Namork@fhi.no} ; H. van Loveren^a ; ^e ; ^{Henk.van.Loveren@RIVM.nl} ; J.H.M. van Delft^a ; ^{J.vanDelft@maastrichtuniversity.nl}
• 关键词：Transcriptomics ; Genotoxicity ; Non-genotoxic carcinogenicity ; Human ; Peripheral blood mononuclear cells ; Biomarker
• 刊名：Mutation Research/Genetic Toxicology and Environmental Mutagenesis
• 出版年：2012
• 期刊代码：31_13835718
• 类别：pha
• 出版时间：15 August, 2012
• 卷：746
• 期：2
• 页码：124-134
• 文件大小：868 K

摘要

For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effect markers provide limited mechanistic insight, and do not allow detection of exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure in human peripheral blood cells (PBMC). Whole genome gene expression changes were investigated following 20 h of in vitro exposure to a high and low concentration of eight genotoxic and three non-genotoxic carcinogenic compounds using whole genome microarrays. Per condition, PBMC of five independent donors were exposed, all in the presence of human liver S9. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic gene sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomarkers of carcinogen exposure.