Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide.

2.50
Hdl Handle:
http://hdl.handle.net/10541/96519
Title:
Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide.
Authors:
Lee, S M; Thatcher, Nick; Crowther, Derek; Margison, Geoffrey P
Abstract:
O6-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.
Affiliation:
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. 1994, 69 (3):452-6 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Mar-1994
URI:
http://hdl.handle.net/10541/96519
PubMed ID:
8123472
PubMed Central ID:
1968858
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLee, S Men
dc.contributor.authorThatcher, Nicken
dc.contributor.authorCrowther, Dereken
dc.contributor.authorMargison, Geoffrey Pen
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.en
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-

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