{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:15:57Z","timestamp":1761718557143},"reference-count":53,"publisher":"ScienceOpen","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>One of the most widely employed histone deacetylases inhibitors in the clinic is the valproic acid (VA), proving to have a good tolerance and low side effects on human health. VA induces changes in chromatin structure making DNA more susceptible to damage induction and influence DNA repair efficiency. VA is also proposed as a radiosensitizing agent. To know if VA is suitable to sensitize human lymphocytes \u03b3-irradiation <jats:italic>in vitro<\/jats:italic>, different types of chromosomal aberrations in the lymphocytes, either in the absence or presence of VA, were analyzed. For this purpose, blood samples from four healthy donors were exposed to \u03b3-rays at a dose of 1.5 Gy and then treated with two different doses of VA (0.35 or 0.70 mM). Unstable and stable chromosomal aberrations were analyzed by means of fluorescence <jats:italic>in situ<\/jats:italic> hybridization. Human lymphocytes treated with VA alone did not show any increase in the frequency of chromosomal aberrations. However, a moderate degree of sensitization was observed, through the increase of chromosomal aberrations, when 0.35 mM VA was employed after \u03b3-irradiation, whereas 0.70 mM VA did not modify chromosomal aberration frequencies. The lower number of chromosomal aberrations obtained when VA was employed at higher dose after \u03b3-irradiation, could be related to the induction of a cell cycle arrest, a fact that should be taken into consideration when VA is employed in combination with physical or chemical agents.<\/jats:p>","DOI":"10.4103\/2041-9414.198909","type":"journal-article","created":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T09:07:49Z","timestamp":1485162469000},"source":"Crossref","is-referenced-by-count":5,"title":["Effects of Valproic Acid on Radiation-Induced Chromosomal Aberrations in Human Lymphocytes"],"prefix":"10.14293","volume":"8","author":[{"given":"Mar\u00eda Vittoria","family":"Di Tomaso","sequence":"first","affiliation":[{"name":"Clemente Estable Biological Research Institute, Montevideo, Uruguay"},{"name":"Laboratoire de Dosim\u00e9trie Biologique, Institut de Radiobiologie et de Suret\u00e9 Nucl\u00e9aire, Fontenay-Aux-Roses, France"},{"name":"Department of Genetics, Clemente Estable Biological Research Institute, Montevideo, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Gregoire","sequence":"additional","affiliation":[{"name":"Laboratoire de Dosim\u00e9trie Biologique, Institut de Radiobiologie et de Suret\u00e9 Nucl\u00e9aire, Fontenay-Aux-Roses, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilner","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Clemente Estable Biological Research Institute, Montevideo, Uruguay"},{"name":"Epigenetics and Genomic Instability Laboratory, Clemente Estable Biological Research Institute, Montevideo, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5403","published-online":{"date-parts":[[2017,1,23]]},"reference":[{"key":"ref1","volume-title":"Chromatin Structure and Function","author":"A Wolffe","year":"1998"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1146\/annurev.biophys.093008.131348","article-title":"Chromatin dynamics","volume":"39","author":"MR H\u00fcbner","year":"2010","journal-title":"Annu Rev Biophys"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.mrrev.2008.01.008","article-title":"Chromatin-remodelling mechanisms in cancer","volume":"658","author":"L Lafon-Hughes","year":"2008","journal-title":"Mutat Res Rev"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000296275","article-title":"Histone post-translational modifications in DNA damage response","volume":"128","author":"L M\u00e9ndez-Acu\u00f1a","year":"2010","journal-title":"Cytogenet Genome Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"AJ Bannister","year":"2011","journal-title":"Cell Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm1963","article-title":"Poly (ADP-ribose): Novel functions for an old molecule","volume":"7","author":"V Schreiber","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1101\/gad.1404206","article-title":"Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications","volume":"20","author":"D Nathan","year":"2006","journal-title":"Genes Dev"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jnutbio.2005.03.025","article-title":"Biological functions of biotinylated histones","volume":"16","author":"N Kothapalli","year":"2005","journal-title":"J Nutr Biochem"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/bies.950190111","article-title":"Histone acetylation: A possible mechanism for the inheritance of cell memory at mitosis","volume":"19","author":"P Jeppesen","year":"1997","journal-title":"Bioessays"},{"key":"ref10","first-page":"1509","article-title":"Role of histone deacetylase inhibitors in the treatment of cancer (Review)","volume":"25","author":"S Mei","year":"2004","journal-title":"Int J Oncol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2165\/00003495-197713020-00001","article-title":"Sodium valproate: A review of its pharmacological properties and therapeutic efficacy in epilepsy","volume":"13","author":"RM Pinder","year":"1977","journal-title":"Drugs"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"R85","DOI":"10.1093\/hmg\/ddi106","article-title":"Histone modifying and chromatin remodelling enzymes in cancer and dysplastic syndromes","volume":"14","author":"RJ Gibbons","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/j.1600-0463.2007.apm_776.xml.x","article-title":"Chromatin-modifying proteins in cancer","volume":"115","author":"CK Fog","year":"2007","journal-title":"APMIS"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/j.1600-0463.2007.apm_636.xml.x","article-title":"Epigenetic changes in cancer","volume":"115","author":"K Gr\u00f8nbaek","year":"2007","journal-title":"APMIS"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"36734","DOI":"10.1074\/jbc.M101287200","article-title":"Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen","volume":"276","author":"CJ Phiel","year":"2001","journal-title":"J Biol Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1007\/s00018-007-7079-x","article-title":"The mechanisms of action of valproate in neuropsychiatric disorders: Can we see the forest for the trees?","volume":"64","author":"G Rosenberg","year":"2007","journal-title":"Cell Mol Life Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/ijc.20774","article-title":"Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid","volume":"114","author":"K Camphausen","year":"2005","journal-title":"Int J Cancer"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1200\/JCO.2007.11.6202","article-title":"Inhibition of histone deacetylation: A strategy for tumor radiosensitization","volume":"25","author":"K Camphausen","year":"2007","journal-title":"J Clin Oncol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"5420","DOI":"10.1038\/sj.onc.1210610","article-title":"Histone deacetylases and cancer","volume":"26","author":"MA Glozak","year":"2007","journal-title":"Oncogene"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1038\/sj.onc.1210599","article-title":"HATs and HDACs: From structure, function and regulation to novel strategies for therapy and prevention","volume":"26","author":"XJ Yang","year":"2007","journal-title":"Oncogene"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"234","DOI":"10.2307\/3577324","article-title":"Chromatin decondensed by acetylation shows an elevated radiation response","volume":"117","author":"Z Nackerdien","year":"1989","journal-title":"Radiat Res"},{"key":"ref22","first-page":"51","article-title":"Chromatin modulation by histone deacetylase inhibitors: Impact on cellular sensitivity to ionizing radiation","volume":"5","author":"F Carrier","year":"2013","journal-title":"Mol Cell Pharmacol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S0300-9084(01)01347-5","article-title":"Chromatin structure and dynamics: Functional implications","volume":"83","author":"V Morales","year":"2001","journal-title":"Biochimie"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1590\/S1415-47572000000400053","article-title":"Interchromosomal distribution of gamma ray-induced chromatid aberrations in Chinese hamster ovary (CHO) cells","volume":"23","author":"W Mart\u00ednez-L\u00f3pez","year":"2000","journal-title":"Genet Mol Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1023\/A:1026747801728","article-title":"Chromosome regions enriched in hyperacetylated histone H4 are preferred sites for endonuclease-and radiation-induced breakpoints","volume":"9","author":"W Mart\u00ednez-L\u00f3pez","year":"2001","journal-title":"Chromosome 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Falk","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1083\/jcb.200704140","article-title":"Global chromatin compaction limits the strength of the DNA damage response","volume":"178","author":"M Murga","year":"2007","journal-title":"J Cell Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"E914","DOI":"10.1073\/pnas.1315684111","article-title":"Radiation dose rates now and in the future for residents neighboring restricted areas of the Fukushima Daiichi Nuclear Power Plant","volume":"111","author":"KH Harada","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref32","volume-title":"International Atomic Energy Agency. Cytogenetic dosimetry: Applications in preparedness for and response to radiation emergencies. EPR-Biodosimetry","year":"2011"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1158\/1535-7163.MCT-06-0022","article-title":"Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci","volume":"5","author":"A Munshi","year":"2006","journal-title":"Mol Cancer Ther"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/251156a0","article-title":"New Giemsa method for the differential staining of sister chromatids","volume":"251","author":"P Perry","year":"1974","journal-title":"Nature"},{"issue":"Pt 1","key":"ref35","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1101\/SQB.1986.051.01.018","article-title":"Cytogenetic analysis by in situ hybridization with fluorescently labeled nucleic acid probes","volume":"51","author":"D Pinkel","year":"1986","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1073\/pnas.83.9.2934","article-title":"Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization","volume":"83","author":"D Pinkel","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1269\/jrr.07013","article-title":"Monitoring translocations by M-FISH and three-color FISH painting techniques: A study of two radiotherapy patients","volume":"48","author":"F Pouzoulet","year":"2007","journal-title":"J Radiat Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000133434","article-title":"Translocations between two specific human chromosomes detected by three-color \u201cchromosome painting\u201d","volume":"62","author":"JN Lucas","year":"1993","journal-title":"Cytogenet Cell Genet"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"7474","DOI":"10.1073\/pnas.88.17.7474","article-title":"Parameters of the human genome","volume":"88","author":"NE Morton","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1158\/0008-5472.CAN-04-2478","article-title":"Valproic acid alters chromatin structure by regulation of chromatin modulation proteins","volume":"65","author":"DC Marchion","year":"2005","journal-title":"Cancer Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/ajh.20273","article-title":"Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?","volume":"78","author":"TE Coyle","year":"2005","journal-title":"Am J Hematol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"5410","DOI":"10.1158\/1078-0432.CCR-08-0643","article-title":"Postradiation sensitization of the histone deacetylase inhibitor valproic acid","volume":"14","author":"P Chinnaiyan","year":"2008","journal-title":"Clin Cancer Res"},{"key":"ref43","first-page":"263","article-title":"HDAC inhibition radiosensitizes human normal tissue cells and reduces DNA Double-Strand Break repair capacity","volume":"23","author":"JC Purrucker","year":"2010","journal-title":"Oncol Rep"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s13148-010-0007-1","article-title":"Targeting the epigenome: Effects of epigenetic treatment strategies on genomic stability in healthy human cells","volume":"1","author":"JC Purrucker","year":"2010","journal-title":"Clin Epigenetics"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/bjc.2013.21","article-title":"Histone deacetylase inhibitors as radiosensitisers: Effects on DNA damage signalling and repair","volume":"108","author":"B Groselj","year":"2013","journal-title":"Br J Cancer"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"4912","DOI":"10.1158\/1078-0432.CCR-04-2088","article-title":"Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity","volume":"11","author":"A Munshi","year":"2005","journal-title":"Clin Cancer Res"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.7164\/antibiotics.53.1191","article-title":"Mechanism of cell cycle arrest caused by histone deacetylase inhibitors in human carcinoma cells","volume":"53","author":"YB Kim","year":"2000","journal-title":"J Antibiot (Tokyo"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.freeradbiomed.2010.11.011","article-title":"Induction of cell cycle arrest and DNA damage by the HDAC inhibitor panobinostat (LBH589) and the lipid peroxidation end product 4-hydroxynonenal in prostate cancer cells","volume":"50","author":"P Pettazzoni","year":"2011","journal-title":"Free Radic Biol Med"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1478-811X-10-1","article-title":"Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity","volume":"10","author":"CS Thiel","year":"2012","journal-title":"Cell Commun Signal"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1196\/annals.1404.014","article-title":"Effect of the histone deacetylase inhibitor trichostatin a in human peripheral blood lymphocytes as a function of donor age","volume":"1119","author":"TG Sourlingas","year":"2007","journal-title":"Ann N Y Acad Sci"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0165-7992(90)90124-3","article-title":"The effect of valproic acid on SCE and chromosome aberrations in epileptic children","volume":"243","author":"LJ Hu","year":"1990","journal-title":"Mutat 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