Abstract
Inappropriate survival signaling after DNA damage may facilitate clonal expansion of genetically compromised cells, and it is known that protein tyrosine phosphatase (PTP) inhibitors activate key survival pathways. In this study we employed the genotoxicant, hexavalent chromium [Cr(VI)], which is a well-documented carcinogen of occupational and environmental concern. Cr(VI) induces a complex array of DNA damage, including DNA double strand breaks (DSBs). We recently reported that PTP inhibition bypassed cell cycle arrest and abrogated Cr(VI)-induced clonogenic lethality. Notably, PTP inhibition resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of DNA damage may lead to genomic instability (GIN), via cell cycle checkpoint bypass. The aim of the present study was to determine the effect of PTP inhibition on DNA DSB formation and chromosomal integrity after Cr(VI) exposure. Diploid human lung fibroblasts were treated with Cr(VI) in the presence or absence of the PTP inhibitor, sodium orthovanadate, for up to 24h, and cells were analyzed for DNA DSBs and chromosomal damage. Cr(VI) treatment induced a rapid increase in DNA DSBs, and a significant increase in...Continue Reading
References
Jan 1, 1992·Mutation Research·J P WiseS R Patierno
Jul 8, 1999·Journal of Cellular Physiology·J Chernoff
May 23, 2002·Carcinogenesis·Stephen P Jackson
May 30, 2002·Mutation Research·John Pierce WiseJennifer E Little
Mar 15, 2003·The Journal of Biological Chemistry·Linan HaSteven R Patierno
Aug 30, 2003·Oncogene·Kristoffer Valerie, Lawrence F Povirk
Dec 4, 2003·Mutation Research·Travis J O'BrienSteven R Patierno
Jul 31, 2004·Carcinogenesis·Linan HaSteven R Patierno
Sep 1, 2004·Cellular and Molecular Life Sciences : CMLS·T C Karagiannis, A El-Osta
May 24, 2005·DNA Repair·Melissa L Hefferin, Alan E Tomkinson
Jun 14, 2005·Experimental Eye Research·Wei-Li ChenNancy C Joyce
Aug 23, 2005·Mutation Research·Hong XieJohn Pierce Wise
Sep 24, 2005·Biochemical and Biophysical Research Communications·Fiona FurlongFinian Martin
Mar 25, 2006·Nature Reviews. Cancer·Arne OstmanFrank D Böhmer
May 23, 2006·Cellular Signalling·Irena Szumiel
Jun 20, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jun MatsumotoJun-ichi Kuratsu
Jun 30, 2006·DNA Repair·Eiichiro SonodaShunichi Takeda
Jul 28, 2006·Mutation Research·Amie L HolmesJohn Pierce Wise
Jul 31, 2007·Mutation Research·Megan M StackpoleJohn Pierce Wise
Jun 19, 2008·Reviews on Environmental Health·Sandra S WiseJohn Pierce Wise
Nov 18, 2008·Mutation Research·Dongsoon BaeSusan Ceryak
Mar 3, 2009·Cancer Biology & Therapy·Sarah E GoldingKristoffer Valerie
Apr 21, 2009·Cell Cycle·Madhu A LalSusan Ceryak
Jul 17, 2009·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·George Iliakis
Jan 22, 2010·Carcinogenesis·Gina ChunSusan Ceryak
Jul 10, 2010·DNA Repair·Malte KriegsEkkehard Dikomey
Jan 1, 2009·F1000 Biology Reports·Aaron A Goodarzi, Penny A Jeggo
Feb 19, 2011·Mutation Research·Emil Mladenov, George Iliakis
Jun 15, 2011·Cell Cycle·Liyan HuWei Dai