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dc.contributor.authorBoddie Jr., A. W.en
dc.contributor.authorConstantinou, Andreas I.en
dc.contributor.authorWilliams, C.en
dc.contributor.authorReed, A.en
dc.date.accessioned2019-11-04T12:50:16Z
dc.date.available2019-11-04T12:50:16Z
dc.date.issued1998
dc.identifier.urihttp://gnosis.library.ucy.ac.cy/handle/7/52954
dc.description.abstractWe hypothesized that unexplained increases in nucleoside triphosphates (NTP) observed by 31P magnetic resonance spectroscopy (MRS) after treatment of tumours by DNA-damaging agents were related to chemotherapy-induced up-regulation of the bcl-2 gene and DNA damage prevention and repair processes. To test this hypothesis, we treated HT-29 cells with 10-4 M nitrogen mustard (HN2) and performed sequential perchloric acid extractions in replicate over 0-18 h. By reference to an internal standard (methylene diphosphonic acid), absolute changes in 31P-detectable high-energy phosphates in these extracts were determined and correlated with changes in bcl-2 protein levels, cell viability, cell cycle, apoptosis and total cellular glutathione (GSH) (an important defence against DNA damage from alkylating agents). After HN2 administration, bcl-2 protein levels in the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but apoptosis measured using fluorescence techniques remained in the 1-4% range. Increased cell division was noted at 4 h. Two high-energy interconvertible phosphates, NTP (P ≤ 0.006) and phosphocreatine (PCr) (P ≤ 0.0002), increased at 2 h concurrently with increased levels of bcl-2 protein and glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased NTP after chemotherapy.en
dc.sourceBritish journal of canceren
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-7144251162&partnerID=40&md5=f6a2cd0586472fa78efa4d0c204e8760
dc.subjectarticleen
dc.subjectchlormethineen
dc.subjecthumanen
dc.subjectHumansen
dc.subjectChemotherapyen
dc.subjectpriority journalen
dc.subjectprotein bcl 2en
dc.subjecthuman cellen
dc.subjectapoptosisen
dc.subjectColonic Neoplasmsen
dc.subjectcell cycleen
dc.subjectUp-Regulationen
dc.subjectMechlorethamineen
dc.subjectMagnetic Resonance Spectroscopyen
dc.subjectfluorescenceen
dc.subjectAmmoniaen
dc.subjectcell viabilityen
dc.subjectBcl-2en
dc.subjectAdenosine Triphosphateen
dc.subjectAntineoplastic Agents, Alkylatingen
dc.subjectATPen
dc.subjectcell divisionen
dc.subjectcell strain ht29en
dc.subjectChromatography, High Pressure Liquiden
dc.subjectcreatine phosphateen
dc.subjectCytidine Triphosphateen
dc.subjectGenes, bcl-2en
dc.subjectGlutathioneen
dc.subjectGuanosine Triphosphateen
dc.subjecthigh energy phosphateen
dc.subjectHT29 Cellsen
dc.subjectNTPen
dc.subjectnucleoside triphosphateen
dc.subjectPhosphocreatineen
dc.subjectPurine Nucleotidesen
dc.subjectUridine Triphosphateen
dc.titleNitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cellsen
dc.typeinfo:eu-repo/semantics/article
dc.description.volume77
dc.description.startingpage1395
dc.description.endingpage1404
dc.type.uhtypeArticleen
dc.description.notes<p>Cited By :8</p>en
dc.source.abbreviationBr.J.Canceren
dc.contributor.orcidConstantinou, Andreas I. [0000-0003-0365-1821]


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