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dc.contributor.authorLee, Siow Ming
dc.contributor.authorThatcher, Nick
dc.contributor.authorMargison, Geoffrey P
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.
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
html.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.


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