Abstract
Assessing the potential carcinogenicity of human toxins represents an ongoing challenge. Chronic rodent bioassays predict human cancer risk with limited reliability, and are expensive and time-consuming. To identify alternative prediction methods, we evaluated a transcriptomics-based human in vitro model to classify carcinogens by their modes of action. The aim of this study was to determine the transcriptomic response and identify specific molecular signatures of polycyclic aromatic hydrocarbons (PAHs), which can be used as predictors of carcinogenicity of environmental toxins in human in vitro systems. We found that characteristic molecular signatures facilitate identification and prediction of carcinogens. To evaluate the change in gene expression levels, human hepatocellular carcinoma (HepG2) cells were exposed to nine different PAHs (benzo[a]pyrene, dibenzo[a,h]anthracene, 3-methylcholanthrene, naphthalene, chrysene, phenanthrene, benzo[a]anthracene, benzo[k]fluoranthene, and indeno[1,2,3-c,d]pyrene) for 48 h. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxin, and a supervised analysis identified 31 outlier genes as distinct molecular signatures distinguishing carcinogens...Continue Reading
References
Jan 1, 1991·Molecular Carcinogenesis·R W TennantR A Griesemer
Dec 16, 1983·Journal of Immunological Methods·T Mosmann
May 1, 1993·Carcinogenesis·I C HsuC C Harris
Sep 1, 1996·Mutation Research·M L Cunningham
Jan 1, 1996·International Archives of Occupational and Environmental Health·L Alessio
Nov 14, 1997·Science·F P Perera
May 23, 1998·Annual Review of Pharmacology and Toxicology·J C DavilaD Acosta
Dec 23, 1998·Environmental Health Perspectives·S NesnowG D Stoner
Apr 16, 1999·Molecular Carcinogenesis·E F NuwaysirC A Afshari
Mar 4, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·J W SpaldingR W Tennant
Jun 3, 2000·Annual Review of Immunology·L M Staudt, P O Brown
Dec 2, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·M E BurczynskiM D Johnson
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Sep 22, 2001·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H M HarriesV A Baker
Jan 24, 2002·Mutation Research·Marilyn J Aardema, James T MacGregor
Jun 8, 2002·Toxicologic Pathology·David A GronebergAxel Fischer
May 2, 2003·The New England Journal of Medicine·Louis M Staudt
Jul 18, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stefan WilkeningAugustinus Bader
May 7, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Samuel M Cohen
May 14, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Abigail Jacobs, David Jacobson-Kram
Jun 24, 2004·Toxicologic Pathology·Richard D IrwinRichard S Paules
Apr 5, 2005·Toxicologic Pathology·Donna M DambachFrederic Moulin
Jun 1, 2005·Mutation Research·J H M van DelftJ C S Kleinjans
Dec 31, 2005·Nucleic Acids Research·Minoru KanehisaMika Hirakawa
Jun 15, 2007·BMC Developmental Biology·Marinus F W Te PasLuc L G Janss
Aug 11, 2007·Mutation Research·Heidrun Ellinger-ZiegelbauerHans Juergen Ahr
Jun 27, 2008·Toxicology·Jung Woo EunSuk Woo Nam
Sep 23, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Karen MathijsJoost H M van Delft
Oct 20, 2010·Toxicology and Applied Pharmacology·Jeong Kyu KimSuk Woo Nam
Jun 4, 2011·Cancer Science·Mi-Kyung SongJae-Chun Ryu
Citations
Nov 8, 2013·Environmental Science and Pollution Research International·Mi-Kyung SongJae-Chun Ryu
Sep 3, 2013·Journal of Hazardous Materials·F Portet-KoltaloC Duclairoir-Poc
Mar 29, 2016·Life Sciences·Kyung Eun KimHyun Jeong Park
Sep 26, 2015·Environmental Toxicology·Yoon ChoJae-Chun Ryu
Sep 18, 2015·Archives of Toxicology·S LabibS Halappanavar
Jun 19, 2015·Mutagenesis·Cheng PengJack C Ng
Jul 5, 2015·International Journal of Hygiene and Environmental Health·Mi-Kyung Song, Jae-Chun Ryu
Apr 25, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Susan C TiltonKatrina M Waters
Jun 27, 2014·Environmental Research·Diego BadernaEmilio Benfenati
Apr 26, 2015·Chemosphere·Ying LiuRainer Lohmann
May 30, 2015·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·C CeccaroliA Izzotti
Aug 6, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M J A JettenJ H M van Delft
Feb 4, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Bénazir SiddeekMohamed Benahmed
Jul 19, 2013·The Science of the Total Environment·Diego BadernaEmilio Benfenati
Dec 8, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Polyxeni TsitouPeter J Boogaard
Aug 3, 2016·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Chie FurihataMadoka Nakajima
Jun 11, 2016·Journal of Applied Toxicology : JAT·Alejandro BarrancoSandra Rainieri
Oct 11, 2017·PloS One·Luca CicaleseCristiana Rastellini
May 19, 2020·Toxicology and Industrial Health·Vicky Nicolaidou, Costas Koufaris
Jun 7, 2019·Environmental Science and Pollution Research International·Arti MishraIndu Shekhar Thakur
Sep 3, 2020·Environmental Science and Pollution Research International·Muhammad Yasir Abdur RehmanJabir Hussain Syed
Sep 6, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yvonne ChangSusan C Tilton
Dec 11, 2020·Journal of Hazardous Materials·Bei WangKin-Fai Ho
Jan 19, 2021·Physiological Genomics·Shu-Lun JiangDong-Po Xu
Jul 12, 2014·Chemical Research in Toxicology·Mi-Kyung SongJae-Chun Ryu
Aug 22, 2021·Environmental Science and Pollution Research International·Chibuisi G AlimbaKannan Krishnamurthi