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dc.contributor.authorLind, Michael J
dc.contributor.authorMcGown, Alan T
dc.contributor.authorHadfield, John A
dc.contributor.authorThatcher, Nick
dc.contributor.authorCrowther, Derek
dc.contributor.authorFox, Brian W
dc.date.accessioned2010-07-22T08:50:46Z
dc.date.available2010-07-22T08:50:46Z
dc.date.issued1989-06-01
dc.identifier.citationThe effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo. 1989, 38 (11):1835-40 Biochem Pharmacolen
dc.identifier.issn0006-2952
dc.identifier.pmid2735940
dc.identifier.urihttp://hdl.handle.net/10541/108137
dc.description.abstractThe effect of ifosfamide and its metabolites on intracellular levels of glutathione in P388 cells in vitro has been studied. It is demonstrated that glutathione depletion occurs only in the presence of 4-hydroperoxyifosfamide and chloroacetaldehyde. In contrast isophosphoramide mustard had no effect on glutathione levels in intact cells. The concentration of 4-hydroperoxyifosfamide required to reduce glutathione levels by 50% was approximately 1 mM and this represents a concentration far in excess of that achievable in patients receiving the drug. However the concentration of chloroacetaldehyde (approximately 100 microM) required to reduce intracellular levels of glutathione to a similar extent is attained in patients receiving ifosfamide. The glutathione levels in lymphocytes isolated from a patient undergoing an eight hour infusion of ifosfamide showed a marked decrease to about 30% of their original value. We conclude that ifosfamide causes glutathione depletion in vivo and the majority of this can be accounted for by the production of chloroacetaldehyde.
dc.language.isoenen
dc.subject.meshAcetaldehyde
dc.subject.meshCell Line
dc.subject.meshGlutathione
dc.subject.meshGlutathione Transferase
dc.subject.meshHumans
dc.subject.meshIfosfamide
dc.subject.meshMacrophages
dc.subject.meshPlacenta
dc.subject.meshTime Factors
dc.titleThe effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, U.K.en
dc.identifier.journalBiochemical Pharmacologyen
html.description.abstractThe effect of ifosfamide and its metabolites on intracellular levels of glutathione in P388 cells in vitro has been studied. It is demonstrated that glutathione depletion occurs only in the presence of 4-hydroperoxyifosfamide and chloroacetaldehyde. In contrast isophosphoramide mustard had no effect on glutathione levels in intact cells. The concentration of 4-hydroperoxyifosfamide required to reduce glutathione levels by 50% was approximately 1 mM and this represents a concentration far in excess of that achievable in patients receiving the drug. However the concentration of chloroacetaldehyde (approximately 100 microM) required to reduce intracellular levels of glutathione to a similar extent is attained in patients receiving ifosfamide. The glutathione levels in lymphocytes isolated from a patient undergoing an eight hour infusion of ifosfamide showed a marked decrease to about 30% of their original value. We conclude that ifosfamide causes glutathione depletion in vivo and the majority of this can be accounted for by the production of chloroacetaldehyde.


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