Development of a toxicogenomics signature for genotoxicity using a dose-optimization and informatics strategy in human cells

Environmental and Molecular Mutagenesis
Heng-Hong LiAlbert J Fornace

Abstract

The development of in vitro molecular biomarkers to accurately predict toxicological effects has become a priority to advance testing strategies for human health risk assessment. The application of in vitro transcriptomic biomarkers promises increased throughput as well as a reduction in animal use. However, the existing protocols for predictive transcriptional signatures do not establish appropriate guidelines for dose selection or account for the fact that toxic agents may have pleiotropic effects. Therefore, comparison of transcriptome profiles across agents and studies has been difficult. Here we present a dataset of transcriptional profiles for TK6 cells exposed to a battery of well-characterized genotoxic and nongenotoxic chemicals. The experimental conditions applied a new dose optimization protocol that was based on evaluating expression changes in several well-characterized stress-response genes using quantitative real-time PCR in preliminary dose-finding studies. The subsequent microarray-based transcriptomic analyses at the optimized dose revealed responses to the test chemicals that were typically complex, often exhibiting substantial overlap in the transcriptional responses between a variety of the agents making an...Continue Reading

References

Aug 1, 1979·Chemico-biological Interactions·R F WhitingD J Koropatnick
Feb 1, 1975·Mutation Research·D WeinsteinS Kazmer
Jun 1, 1991·Journal of Applied Toxicology : JAT·Y OshiroS G Soelter
Oct 1, 1989·Molecular and Cellular Biology·A J FornaceN J Holbrook
Oct 1, 1986·Proceedings of the Society for Experimental Biology and Medicine·A SegalA C Upton
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A J FornaceM C Hollander
Jan 1, 1988·Environmental and Molecular Mutagenesis·E ZeigerK Mortelmans
May 1, 1984·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·T J Hansen
Sep 1, 1981·Chemico-biological Interactions·A J FornaceC C Harris
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·G GetzE Domany
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Robert TibshiraniGilbert Chu
Mar 23, 2004·Environmental Health Perspectives·Ronald K NewtonJiri Aubrecht
Oct 30, 2004·Environmental and Molecular Mutagenesis·Mohammed IslaihRonald K Newton
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 1, 2007·Chemical Research in Toxicology·Konstantin Salnikow, Anatoly Zhitkovich
Apr 24, 2008·Nature Reviews. Molecular Cell Biology·Todd RileyArnold Levine
May 26, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Heidrun Ellinger-ZiegelbauerJiri Aubrecht
Mar 31, 2010·Pharmacogenomics·Yuxia Cui, Richard S Paules
Jun 2, 2010·Nature Reviews. Drug Discovery·Federico M GoodsaidIssam Zineh
Aug 27, 2010·Environmental and Molecular Mutagenesis·Anthony M LynchJames H Kim
Feb 8, 2011·Toxicology and Applied Pharmacology·Vickie S WilsonSusan Y Euling
Jun 1, 2011·ALTEX·Thomas Hartung, Mary McBride

❮ Previous
Next ❯

Citations

Jan 15, 2016·Environmental and Molecular Mutagenesis·Steven M BryceStephen D Dertinger
Oct 27, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nikolai L ChepelevCarole L Yauk
May 5, 2016·Critical Reviews in Toxicology·Mirjam LuijtenJan van Benthem
Aug 25, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Raffaella Corvi, Federica Madia
Dec 6, 2017·Proceedings of the National Academy of Sciences of the United States of America·Heng-Hong LiAlbert J Fornace
Nov 7, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Steven M BryceStephen D Dertinger
Oct 18, 2018·Environmental and Molecular Mutagenesis·J Christopher CortonCarole L Yauk
Feb 11, 2020·Environmental and Molecular Mutagenesis·Shuchang TianStephen D Dertinger
Apr 4, 2017·Environmental and Molecular Mutagenesis·Steven M BryceStephen D Dertinger
Jun 25, 2017·Environmental and Molecular Mutagenesis·Stephen D Dertinger
Feb 12, 2020·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Julie K BuickCarole L Yauk
Mar 20, 2018·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Patrícia L AbreuAna M Urbano
Nov 20, 2016·Environmental and Molecular Mutagenesis·Mirjam LuijtenJan van Benthem
Apr 3, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Katrin KreuzerAlbert Braeuning
Jun 27, 2021·Regulatory Toxicology and Pharmacology : RTP·Susan J BorghoffGrace A Chappell
Jul 14, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jeliyah ClarkJulia E Rager
Aug 10, 2019·Chemical Research in Toxicology·J Christopher CortonCarole L Yauk
Nov 10, 2021·Nucleic Acids Research·Cari MartiniJennifer Fostel

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.