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dc.contributor.authorLee, S M
dc.contributor.authorThatcher, Nick
dc.contributor.authorCrowther, Derek
dc.contributor.authorMargison, Geoffrey P
dc.date.accessioned2010-04-14T11:43:43Z
dc.date.available2010-04-14T11:43:43Z
dc.date.issued1994-03
dc.identifier.citationInactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. 1994, 69 (3):452-6 Br. J. Canceren
dc.identifier.issn0007-0920
dc.identifier.pmid8123472
dc.identifier.urihttp://hdl.handle.net/10541/96519
dc.description.abstractO6-alkylguanine-DNA-alkyltransferase (ATase) activity was measured in extracts of peripheral blood mononuclear cells (PMCs) taken from eight patients at various times during 5 days of oral treatment with temozolomide (150 mg m-2, days 1-5). Pretreatment ATase levels ranged from approximately 70 to 600 fmol per mg of protein. Depletion of PMC ATase was seen within 4 h of the first dose of temozolomide and had a median nadir of 52.9% and values ranging from 44.4% to 71.0% of pretreatment levels. There was a correlation between the extent of ATase depletion (pretreatment minus nadir level) and the pretreatment ATase level (r = 0.97). A progressive depletion of ATase was observed during the 5 days of continuous temozolomide therapy with median ATase activities of 66.3%, 52.5%, 39.5%, 30.5% and 28.9% of the pretreatment values at days 2, 3, 4, 5 and 6 respectively. This suggests that the schedule-dependent anti-tumour activity of temozolomide seen in experimental models and clinics may be related to a cumulative depletion of ATase.
dc.language.isoenen
dc.subjectCancer Metastasis
dc.subject.meshAdministration, Oral
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAntineoplastic Agents
dc.subject.meshDacarbazine
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshKinetics
dc.subject.meshLeukocytes, Mononuclear
dc.subject.meshMale
dc.subject.meshMelanoma
dc.subject.meshMethyltransferases
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Metastasis
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshTime Factors
dc.titleInactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren
dc.identifier.pmcid1968858
html.description.abstractO6-alkylguanine-DNA-alkyltransferase (ATase) activity was measured in extracts of peripheral blood mononuclear cells (PMCs) taken from eight patients at various times during 5 days of oral treatment with temozolomide (150 mg m-2, days 1-5). Pretreatment ATase levels ranged from approximately 70 to 600 fmol per mg of protein. Depletion of PMC ATase was seen within 4 h of the first dose of temozolomide and had a median nadir of 52.9% and values ranging from 44.4% to 71.0% of pretreatment levels. There was a correlation between the extent of ATase depletion (pretreatment minus nadir level) and the pretreatment ATase level (r = 0.97). A progressive depletion of ATase was observed during the 5 days of continuous temozolomide therapy with median ATase activities of 66.3%, 52.5%, 39.5%, 30.5% and 28.9% of the pretreatment values at days 2, 3, 4, 5 and 6 respectively. This suggests that the schedule-dependent anti-tumour activity of temozolomide seen in experimental models and clinics may be related to a cumulative depletion of ATase.


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