Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human lymphoblastoid cell lines that are part of the NIHPDR exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to identify novel predictors of resistance to DNA damaging agents

ABSTRACT: We have investigated whether gene expression signatures can be used to predict inter-individual responses to DNA damaging agents; We used microarrays to detail inter-individual variation in gene expression across a healthy population under basal and damage induced conditions Experiment Overall Design: lymphoblastoid cell lines that are part of the NIHPDR were examine for gene expression differences as well as killing upon exposure to MNNG

ORGANISM(S): Homo sapiens

SUBMITTER: Rebecca Fry

PROVIDER: E-GEOD-10313 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genomic predictors of interindividual differences in response to DNA damaging agents.

Fry Rebecca C RC Svensson J Peter JP Valiathan Chandni C Wang Emma E Hogan Brad J BJ Bhattacharya Sanchita S Bugni James M JM Whittaker Charles A CA Samson Leona D LD

Genes & development 20080919 19

Human lymphoblastoid cells derived from different healthy individuals display considerable variation in their transcription profiles. Here we show that such variation in gene expression underlies interindividual susceptibility to DNA damaging agents. The results demonstrate the massive differences in sensitivity across a diverse cell line panel exposed to an alkylating agent. Computational models identified 48 genes with basal expression that predicts susceptibility with 94% accuracy. Modulating ...[more]

PMID: 18805990

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Project description:The alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a direct mutagen and carcinogen, causing DNA damage and other comprehensive alterations that lead to chromosomal aberrations, mutations, tumor initiation, and cell death. Our previous study revealed that MNNG at different concentrations could induce extensive changes in gene expression at an early stage of exposure. To further understand the dynamic cellular responses and hazardous effects caused by this environmental carcinogen, we used a whole-genome time-course screening methods to find out the gene expression changes induced by a low concentration of MNNG in human normal amnion epithelial FL cells. The cells were exposed to 1.0 M-BM-5M MNNG, and differential gene expression profiles at 3, 12, and 24 h after MNNG treatment were obtained by use of Affymetrix HG-U133 Plus 2.0 oligonucleotide microarray technology, followed by quantitative real-time RT-PCR validation. The results showed that the low-dose MNNG exposure triggered extensive but moderate changes in gene expression at these three experiment time points after exposure. The responsive genes encode important proteins, including cell cycle regulators, transcription factors and signal transducers that determine cell cycle progression, cell fate and other activities associate with pro-oncogenic potentials. The differential gene expression profiles at the three time points varied greatly, and generally reflected a cellular responsive process from initiation to progression and to recovery after MNNG exposure. These results will aid our understanding of the complicated mechanisms of MNNG-induced cellular responses. KeywordsM-oM-<M-^ZN-methyl-N'-nitro-N-nitrosoguanidine; Cellular response; Temporal gene expression change; Oligonucleotide microarray; Quantitative real-time RT-PCR Human amnion epithelial FL cells were exposed to vehicle control (dimethyl sulfoxide) and a low concentration (1.0 M-BM-5M) MNNG for 2 h, respectively. The differential gene expression profiles at 3, 12 and 24 h post MNNG treatment were obtained using Affymetrix HG-U133 Plus 2.0 oligonucleotide microarrays. The transcriptomic changes at different time points post MNNG treatment would provide insight into the dynamic processes of cellular response to this genotoxic agent.

Dataset Information

Transcription profiling of human lymphoblastoid cell lines that are part of the NIHPDR exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to identify novel predictors of resistance to DNA damaging agents

Publications

Genomic predictors of interindividual differences in response to DNA damaging agents.

Similar Datasets

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