Assessment of DNA double-strand breaks and gammaH2AX induced by the topoisomerase II poisons etoposide and mitoxantrone.

Mutation Research
Daniel J SmartGary M Williams

Abstract

Double-strand breaks (DSBs) are highly deleterious DNA lesions as they lead to chromosome aberrations and/or apoptosis. The formation of nuclear DSBs triggers phosphorylation of histone H2AX on Ser-139 (defined as gammaH2AX), which participates in the repair of such DNA damage. Our aim was to compare the induction of gammaH2AX in relation to DSBs induced by topoisomerase II (TOPO II) poisons, etoposide (ETOP) and mitoxantrone (MXT), in V79 cells. DSBs were measured by the neutral comet assay, while gammaH2AX was quantified using immunocytochemistry and flow cytometry. Stabilized cleavage complexes (SCCs), lesions thought to be responsible for TOPO II poison-induced genotoxicity, were measured using a complex of enzyme-DNA assay. In the case of ETOP, a no observed adverse effect level (NOAEL) and lowest observed effect level (LOEL) for genotoxicity was determined; gammaH2AX levels paralleled DSBs at all concentrations but significant DNA damage was not detected below 0.5 microg/ml. Furthermore, DNA damage was dependent on the formation of SCCs. In contrast, at low MXT concentrations (0.0001-0.001 microg/ml), induction of gammaH2AX was not accompanied by increases in DSBs. Rather, DSBs were only significantly increased when SCCs ...Continue Reading

References

Feb 1, 1992·Experimental Cell Research·P L OliveJ P Banáth
Dec 15, 1985·Biochemical Pharmacology·J Kapuscinski, Z Darzynkiewicz
Feb 1, 1995·Mutation Research·D W FairbairnK L O'Neill
Apr 29, 1997·Mutation Research·A R CollinsR Stĕtina
Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Sep 28, 1998·Biochimica Et Biophysica Acta·J M Berger
Sep 28, 1998·Biochimica Et Biophysica Acta·D A Burden, N Osheroff
Oct 13, 1998·Toxicology·J A Timbrell
Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Jul 25, 2000·Toxicology Letters·G Boos, H Stopper
Oct 26, 2000·Nature·T RichA H Wyllie
Feb 13, 2001·Regulatory Toxicology and Pharmacology : RTP·G M Williams, A M Jeffrey
Sep 8, 2001·The Journal of Biological Chemistry·Y MaoL F Liu
Oct 3, 2002·Cellular Signalling·Fayza DaboussiBernard S Lopez
Jul 9, 2003·Immunological Reviews·Kevin D MillsFrederick W Alt
Jul 25, 2003·Cancer Biology & Therapy·Olga A SedelnikovaWilliam M Bonner
Aug 29, 2003·International Journal of Radiation Biology·S H MacPhailP L Olive
Jan 9, 2004·Cell Cycle·Craig H Bassing, Frederick W Alt
Sep 27, 2005·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Akira KuroseZbigniew Darzynkiewicz
Jun 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Thomas M MartiJames E Cleaver
Jul 5, 2006·Molecular Cancer Therapeutics·Mobeen MalikJohn L Nitiss
Aug 24, 2006·Journal of Cellular Biochemistry·Shaun P Scott, Tej K Pandita
Mar 24, 2007·International Journal of Radiation Biology·Iraimoudi S AyeneRobert E Krisch
Jun 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Anna M AzarovaLeroy F Liu

❮ Previous
Next ❯

Citations

Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sebastien de FeraudyJames E Cleaver
May 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ingrid RevetJames E Cleaver
Mar 20, 2009·Molecular Biology of the Cell·Josef Loidl, Kazufumi Mochizuki
Dec 14, 2011·Mutagenesis·Daniel J Smart, Anthony M Lynch
Feb 13, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kirsten E RakkestadRune Becher
May 2, 2014·Ecotoxicology and Environmental Safety·Marko GerićVera Garaj-Vrhovac
Jul 22, 2014·Micron : the International Research and Review Journal for Microscopy·Wojtczak Agnieszka
Sep 18, 2010·Journal of Nucleic Acids·Nicola J SunterCaroline A Austin
Jan 22, 2015·Molecular Medicine Reports·Shanshan ShiShenglin Ma
Oct 7, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Mio IshihamaYuko Ibuki
Apr 18, 2009·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Dec 6, 2011·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Dec 15, 2010·The Journal of Investigative Dermatology·Jennifer L RizzoThomas M Rünger
Apr 23, 2013·Cellular & Molecular Biology Letters·Grzegorz StasiłojćJacek Jerzy Bigda
Nov 10, 2012·Critical Reviews in Clinical Laboratory Sciences·Zbigniew DarzynkiewiczDonald Wlodkowic
Jun 9, 2016·International Journal of Molecular Sciences·Jarline EncarnaciónJaime L Matta
Apr 22, 2009·Mutation Research·Daniel P BezerraLetícia V Costa-Lotufo
Jun 28, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Carolina Garcia-CantonClive Meredith
Jul 23, 2008·Mutagenesis·Lucy C RichesNigel J Gooderham
Jan 6, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Deepak GurbaniAlok Dhawan
Sep 22, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yan LiJin Ren
Feb 2, 2015·Journal of Hazardous Materials·Alfredo ParrellaMarina Isidori
Jan 4, 2017·Bioorganic & Medicinal Chemistry Letters·Idaira Hueso-FalcónAna Estévez-Braun
Sep 2, 2011·Journal of Applied Toxicology : JAT·Meena MahmoodAlexandru S Biris
Jan 10, 2020·Reproductive Sciences·Robert StobezkiKutluk Oktay

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis