O6-alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine.

2.50
Hdl Handle:
http://hdl.handle.net/10541/107856
Title:
O6-alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine.
Authors:
Lee, Siow Ming; Thatcher, Nick; Margison, Geoffrey P
Abstract:
O6-Alkylguanine-DNA alkyltransferase (ATase) levels were measured in peripheral blood lymphocytes of 13 patients with advanced malignant melanoma treated with sequential dacarbazine (DTIC) and fotemustine. Wide interindividual variation in the pretreatment levels and in depletion and regeneration of ATase activity was noted. Depletion of ATase was seen within the first h after DTIC administration with values ranging from 44 to 92% of pretreatment levels. In 10 patients, progressive depletion of ATase activity occurred with nadir activity occurring at about 4 to 6 h with values ranging from 0 to 67% of pretreatment activity; at 18 h after DTIC infusion. ATase activity varied from 6 to 81%. No significant difference was seen between the rates of ATase depletion or regeneration between the two groups of patients receiving either 500 or 800 mg/m2 of DTIC with the same dose of fotemustine (100 mg/m2). In one patient, maximum depletion occurred within 1 h and no ATase activity was detectable over the next 18 h. In another patient, maximum depletion occurred at 2 h after DTIC followed by recovery of ATase activity to 71% at 18 h. In 2 patients who returned for subsequent cycles of chemotherapy, an increase in pretreatment ATase activity was seen. Overall, the extent of depletion of ATase following DTIC/fotemustine was directly proportional to the initial ATase level.
Affiliation:
Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom.
Citation:
O6-alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine. 1991, 51 (2):619-23 Cancer Res.
Journal:
Cancer Research
Issue Date:
15-Jan-1991
URI:
http://hdl.handle.net/10541/107856
PubMed ID:
1824685
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLee, Siow Mingen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-07-17T11:08:54Z-
dc.date.available2010-07-17T11:08:54Z-
dc.date.issued1991-01-15-
dc.identifier.citationO6-alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine. 1991, 51 (2):619-23 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid1824685-
dc.identifier.urihttp://hdl.handle.net/10541/107856-
dc.description.abstractO6-Alkylguanine-DNA alkyltransferase (ATase) levels were measured in peripheral blood lymphocytes of 13 patients with advanced malignant melanoma treated with sequential dacarbazine (DTIC) and fotemustine. Wide interindividual variation in the pretreatment levels and in depletion and regeneration of ATase activity was noted. Depletion of ATase was seen within the first h after DTIC administration with values ranging from 44 to 92% of pretreatment levels. In 10 patients, progressive depletion of ATase activity occurred with nadir activity occurring at about 4 to 6 h with values ranging from 0 to 67% of pretreatment activity; at 18 h after DTIC infusion. ATase activity varied from 6 to 81%. No significant difference was seen between the rates of ATase depletion or regeneration between the two groups of patients receiving either 500 or 800 mg/m2 of DTIC with the same dose of fotemustine (100 mg/m2). In one patient, maximum depletion occurred within 1 h and no ATase activity was detectable over the next 18 h. In another patient, maximum depletion occurred at 2 h after DTIC followed by recovery of ATase activity to 71% at 18 h. In 2 patients who returned for subsequent cycles of chemotherapy, an increase in pretreatment ATase activity was seen. Overall, the extent of depletion of ATase following DTIC/fotemustine was directly proportional to the initial ATase level.en
dc.language.isoenen
dc.subject.meshAdenosine Triphosphatases-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshDacarbazine-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshKinetics-
dc.subject.meshLymphocytes-
dc.subject.meshMale-
dc.subject.meshMelanoma-
dc.subject.meshMethyltransferases-
dc.subject.meshMiddle Aged-
dc.subject.meshNitrosourea Compounds-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshOrganophosphorus Compounds-
dc.titleO6-alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom.en
dc.identifier.journalCancer Researchen
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