Kinetics of γH2AX and phospho-histone H3 following pulse treatment of TK6 cells provides insights into clastogenic activity.

Mutagenesis
Steven M BryceJeffrey C Bemis

Abstract

The desire for in vitro genotoxicity assays to provide higher information content, especially regarding chemicals' predominant genotoxic mode of action, has led to the development of a novel multiplexed assay available under the trade name MultiFlow®. We report here on an experimental design variation that provides further insight into clastogens' genotoxic activity. First, the standard MultiFlow DNA Damage Assay-p53, γ H2AX, phospho-histone H3 was used with human TK6 lymphoblastoid cells that were exposed for 24 continuous hours to each of 50 reference clastogens. This initial analysis correctly identified 48/50 compounds as clastogenic. These 48 compounds were then evaluated using a short-term, 'pulse' treatment protocol whereby cells were exposed to test chemical for 4 h, a centrifugation/washout step was performed, and cells were allowed to recover for 20 h. MultiFlow analyses were accomplished at 4 and 24 h. The γ H2AX and phospho-histone H3 biomarkers were found to exhibit distinct differences in terms of their persistence across chemical classes. Unsupervised hierarchical clustering analysis identified three groups. Examination of the compounds within these groups showed one cluster primarily consisting of alkylators tha...Continue Reading

References

Mar 1, 1991·Antimicrobial Agents and Chemotherapy·A BredbergM Jaszyk
Jan 1, 1991·Environmental and Molecular Mutagenesis·M B St ClairL Recio
Sep 5, 1998·Mutation Research·W F MorganB Ponnaiya
Sep 15, 2000·Mutation Research·E Y Ben-OzerH R Petty
Oct 16, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yoko KashidaKunitoshi Mitsumori
May 14, 2003·Mutation Research·Nilüfer Aydemir, Rahmi Bilaloğlu
Jul 24, 2003·Rapid Communications in Mass Spectrometry : RCM·Birgit PaulssonMargareta Törnqvist
Feb 6, 2007·British Medical Bulletin·Peter Karran
Apr 7, 2007·Journal of Natural Products·Miguel López-LazaroCaroline A Austin
Mar 25, 2008·Chemico-biological Interactions·Lihan LuoLaifu Zhong
Nov 13, 2008·Free Radical Biology & Medicine·Christopher M CabelloGeorg T Wondrak
Jan 20, 2009·Environmental and Molecular Mutagenesis·Sabry M AttiaOthman A Al-Shabanah
Apr 21, 2009·Mutation Research·Elmar Gocke, Lutz Müller
Sep 22, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yan LiJin Ren
Sep 28, 2010·Environmental and Molecular Mutagenesis·Ronald D Snyder
Nov 5, 2011·Environmental and Molecular Mutagenesis·Stephen D DertingerJames T MacGregor
Aug 28, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Stephen D DertingerJames T Macgregor
May 16, 2013·PloS One·Lya G HernándezGeorge E Johnson
Oct 12, 2013·Drug Design, Development and Therapy·Veda PrachayasittikulVirapong Prachayasittikul
Jan 6, 2016·International Journal of Environmental Research and Public Health·Anthony SkipperPaul B Tchounwou
Jan 15, 2016·Environmental and Molecular Mutagenesis·Steven M BryceStephen D Dertinger
Jan 18, 2016·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·David KirklandRaffaella Corvi
Jul 2, 2016·Environmental and Molecular Mutagenesis·Derek T BernackiStephen D Dertinger
Jul 29, 2016·Journal of Cellular and Molecular Medicine·Laurent Ah-KoonOlivier Schischmanoff
Apr 4, 2017·Environmental and Molecular Mutagenesis·Steven M BryceStephen D Dertinger
May 13, 2017·Nucleosides, Nucleotides & Nucleic Acids·Olga V KirsanovaElizaveta S Gromova
Dec 6, 2017·Proceedings of the National Academy of Sciences of the United States of America·Heng-Hong LiAlbert J Fornace
Mar 21, 2018·Mutation Research. Reviews in Mutation Research·Alejandro D Bolzán, Martha S Bianchi
Oct 6, 2018·Biochemical Society Transactions·Jessica L BarnesFrancis L Martin
May 28, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Derek T BernackiStephen D Dertinger
Jul 11, 2019·Archives of Toxicology·B KoppMarc Audebert
Jun 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xiaohang QiaoJacques Neefjes
Jul 4, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Inger BrandsmaGiel Hendriks

❮ 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.