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| Status |
Public on Dec 01, 2010 |
| Title |
Whole genome gene expression modifications associated with micronucleus formation in blood cells from nitrosamine-exposed humans |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
N-nitroso compounds (NOCs) can be formed through endogenous nitrosation in the human body and are known to induce micronuclei (MN) formation in vitro. Since lymphocytic MN represent a well-validated biomarker of effect with regard to carcinogenic risk in multiple target organs, establishing a link between NOCs and MN in humans could provide evidence for a carcinogenic risk. Investigating gene expression modulations in relation to NOC exposure could provide further crucial information on underlying molecular mechanisms-of-action. The purpose of this study is therefore to establish the relationship between human NOC exposure under daily life conditions and MN formation in relation to associated transcriptomic changes, using lymphocytes as a surrogate tissue for analyzing carcinogenic events in target organs. We analyzed gene expression levels and MN frequency in lymphocytes from adults participating in a European cohort from the multidisciplinary research project NewGeneris. For assessing exposure to NOCs, urinary samples were analyzed for marker nitrosamines by GC-MS. NOC exposure was subsequently linked to peripheral blood transcriptomics. We found an association between MN frequency and urinary NOCs, indicating that NOC exposure under daily life circumstances may play an important role in human cancer development. Furthermore, we have identified modifications in pathways which indicate a molecular response to NOC-induced genotoxicity. From this, we derived a small group of genes which could be suitable as mechanistic-based transcriptomic biomarkers of NOC exposure-related cancer risk. The modified genetic processes and genes found in this study may be of interest for future investigations into NOC-associated carcinogenicity in humans.
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| Overall design |
The study investigated transcription levels in human whole blood from 30 pregnant mothers in a Danish NewGeneris cohort. For each subject, cRNA copies of isolated mRNA were labeled with one dye (Cy3) and each sample was hybridized on separate arrays. One replicate per subject (so 30 arrays in total).
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| Contributor(s) |
Hebels DG, Jennen DG, van Herwijnen MH, Moonen EJ, Pedersen M, Knudsen LE, Kleinjans JC, de Kok TM |
| Citation(s) |
21724973 |
| Submission date |
Sep 01, 2010 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Dennie Hebels |
| E-mail(s) |
d.hebels@maastrichtuniversity.nl
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| Phone |
0031-43-3881088
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| Fax |
0031-43-3884146
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| URL |
http://www.grat.nl
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| Organization name |
Maastricht University
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| Department |
Health Risk Analysis and Toxicology
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| Street address |
Universiteitssingel 50
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| City |
Maastricht |
| ZIP/Postal code |
6200MD |
| Country |
Netherlands |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA130521 |
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