Time series analysis of benzo[A]pyrene-induced transcriptome changes suggests that a network of transcription factors regulates the effects on functional gene sets

Toxicological Sciences : an Official Journal of the Society of Toxicology
Joost van DelftJos C Kleinjans

Abstract

Chemical carcinogens may cause a multitude of effects inside cells, thereby affecting transcript levels of genes by direct activation of transcription factors (TF) or indirectly through the formation of DNA damage. As the temporal profiles of these responses may be profoundly different, examining time-dependent changes may provide new insights in TF networks related to cellular responses to chemical carcinogens. Therefore, we investigated in human hepatoma cells gene expression changes caused by benzo[a]pyrene at 12 time points after exposure, in relation to DNA adduct and cell cycle. Temporal profiles for functional gene sets demonstrate both early and late effects in up- and downregulation of relevant gene sets involved in cell cycle, apoptosis, DNA repair, and metabolism of amino acids and lipids. Many significant transcription regulation networks appeared to be around TF that are proto-oncogenes or tumor suppressor genes. The time series analysis tool Short Time-series Expression Miner (STEM) was used to identify time-dependent correlation of pathways, gene sets, TF networks, and biological parameters. Most correlations are with DNA adduct levels, which is an early response, and less with the later responses on G1 and S pha...Continue Reading

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Citations

Feb 10, 2012·Chemical Research in Toxicology·Daneida LizarragaJoost H M van Delft
Aug 24, 2012·Mutagenesis·Maria TsamouJoost H M van Delft
Aug 15, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Joost van DelftJos Kleinjans
Nov 5, 2014·Journal of Proteome Research·Stefan KalkhofMartin von Bergen
Sep 12, 2015·Chemical Research in Toxicology·Danyel G J JennenJos C S Kleinjans
Jan 22, 2015·Critical Reviews in Toxicology·Nikolai L ChepelevCarole L Yauk
Jun 20, 2015·Journal of Toxicology and Environmental Health. Part a·Marjory MoreauMichèle Bouchard
Jun 12, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ariane VettorazziAdela López de Cerain
Dec 17, 2014·Journal of Toxicology and Environmental Health. Part a·Marjory MoreauMichèle Bouchard
Dec 23, 2020·Environmental Toxicology·Suyane da Silva MoreiraArielle Cristina Arena
Nov 22, 2017·Environmental Science & Technology·Xiangsheng HongZijian Wang

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