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Series GSE14284 Query DataSets for GSE14284
Status Public on Apr 01, 2009
Title Molecular signatures of N-nitroso compounds in Caco-2 cells: implications for colon carcinogenesis
Organism Homo sapiens
Experiment type Expression profiling by array
Summary N-nitroso compounds (NOC) are genotoxic compounds and animal carcinogens, and may play a role in human cancer development. Since the gastro-intestinal tract is an important route of exposure, we hypothesize that NOC exposure targets genetic processes relevant in colon carcinogenesis. To investigate this, we analysed the transcriptomic effects of genotoxic concentrations of two nitrosamides, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 1µM) and N-methyl-N-nitrosurea (MNU, 1mM), and four nitrosamines, N-nitrosodiethylamine (NDEA, 50mM), N-nitrosodimethylamine (NDMA, 100mM), N-nitrosopiperidine (NPIP, 40mM), and N-nitrosopyrrolidine (NPYR, 100mM), in the human colon carcinoma cell line Caco-2. Gene Ontology gene group, consensus motif gene group and biological pathway analysis revealed that nitrosamides had little effect on gene expression after 24 hours of exposure, whereas nitrosamines had a strong impact on the transcriptomic profile. Analyses showed modifications of cell cycle regulation and apoptosis pathways for nitrosamines which was supported by flow cytometric analysis. We found additional modifications in gene groups and pathways of oxidative stress and inflammation, which suggest an increase in oxidative stress and pro-inflammatory immune response upon nitrosamine exposure, although less distinct for NDMA. Furthermore, NDEA, NPIP and NPYR most strongly affected several developmental motif gene groups and pathways, which may influence developmental processes. Many of these pathways and gene groups are implicated in the carcinogenic process and their modulation by nitrosamine exposure may therefore influence the development of colon cancer. In summary, our study has identified pathway modifications in human colon cells which may be associated with cancer risk of nitrosamine exposure in the human colon.

Keywords: Comparison of genome-wide gene expression between different conditions
 
Overall design The study investigated differential gene expression in Caco-2 cell line mRNA following 24 hours of exposure to six different N-nitroso compounds. Four biological replicates per sample compound. One compound per array, hybridized against vehicle control. Dye-swap between biological replicates 1 and 2, and 3 and 4.
 
Contributor(s) Hebels DG, Jennen DD, Kleinjans JC, de Kok TM
Citation(s) 19221148, 20403970
Submission date Jan 05, 2009
Last update date Jan 23, 2019
Contact name Dennie Hebels
E-mail(s) d.hebels@maastrichtuniversity.nl
Phone 0031-43-3881088
Fax 0031-43-3884146
URL http://www.grat.nl
Organization name Maastricht University
Department Health Risk Analysis and Toxicology
Street address Universiteitssingel 50
City Maastricht
ZIP/Postal code 6200MD
Country Netherlands
 
Platforms (1)
GPL6480 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)
Samples (24)
GSM357352 MNNG biological replicate 1
GSM357353 MNNG biological replicate 2
GSM357354 MNNG biological replicate 3
Relations
BioProject PRJNA111277

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE14284_RAW.tar 203.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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