Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86665
Title:
Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells.
Authors:
Clemons, Mark; Watson, Amanda J; Howell, Anthony ( 0000-0002-3879-5991 ) ; Chang, James; Heyworth, Clare M; Lord, Brian I; Testa, Nydia G; Dexter, T Michael; Margison, Geoffrey P
Abstract:
Macrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine that may act principally by preventing hemopoietic cells from entering G1, thereby attenuating the cytotoxic effects of cell cycle-specific chemotherapeutic agents. Here we examine the effect of MIP-1alpha on the sensitivity of human granulocyte-macrophage hemopoietic progenitor cells (granulocyte-macrophage colony-forming cells; GM-CFCs) with the cytotoxic effects of antitumor agents that act mainly via alkylation at the O6 position of guanine in DNA. Mononuclear cell preparations from human bone marrow were used in an in vitro GM-CFC colony-forming assay. The GM-CFC survival from individual patients displayed a range of sensitivities to the methylating agent temozolomide [(Tz) 20-55% survival at 10 microg/ml Tz]. However, in all 16 cases, MIP-1alpha (50 ng/ml) protected against GM-CFC killing: survival in the presence of MIP-1alpha ranged from 65-97% at 10 microg/ml Tz, with GM-CFCs being 1.5-4.5-fold more resistant than control cells from the same patient. The highest levels of protection were seen in the GM-CFCs with the highest sensitivity in the absence of MIP-1alpha. Similar degrees of protection were seen for the methylating agent streptozotocin, but no protection was detected for the chloroethylating agents carmustine or mitozolomide in the samples for which there was protection against the toxic effects of Tz. Whereas the mechanism of this effect remains to be established, the results may have potential immediate clinical application in the attenuation of hematological toxicity after administration of methylating antitumor agents.
Affiliation:
Cancer Research Campaign Department of Medical Oncology, Manchester, United Kingdom. markclemons@sprint.ca
Citation:
Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells. 2000, 6 (3):966-70 Clin. Cancer Res.
Journal:
Clinical Cancer Research
Issue Date:
Mar-2000
URI:
http://hdl.handle.net/10541/86665
PubMed ID:
10741722
Type:
Article
Language:
en
ISSN:
1078-0432
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorClemons, Marken
dc.contributor.authorWatson, Amanda Jen
dc.contributor.authorHowell, Anthonyen
dc.contributor.authorChang, Jamesen
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorLord, Brian Ien
dc.contributor.authorTesta, Nydia Gen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2009-11-23T11:32:06Z-
dc.date.available2009-11-23T11:32:06Z-
dc.date.issued2000-03-
dc.identifier.citationMacrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells. 2000, 6 (3):966-70 Clin. Cancer Res.en
dc.identifier.issn1078-0432-
dc.identifier.pmid10741722-
dc.identifier.urihttp://hdl.handle.net/10541/86665-
dc.description.abstractMacrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine that may act principally by preventing hemopoietic cells from entering G1, thereby attenuating the cytotoxic effects of cell cycle-specific chemotherapeutic agents. Here we examine the effect of MIP-1alpha on the sensitivity of human granulocyte-macrophage hemopoietic progenitor cells (granulocyte-macrophage colony-forming cells; GM-CFCs) with the cytotoxic effects of antitumor agents that act mainly via alkylation at the O6 position of guanine in DNA. Mononuclear cell preparations from human bone marrow were used in an in vitro GM-CFC colony-forming assay. The GM-CFC survival from individual patients displayed a range of sensitivities to the methylating agent temozolomide [(Tz) 20-55% survival at 10 microg/ml Tz]. However, in all 16 cases, MIP-1alpha (50 ng/ml) protected against GM-CFC killing: survival in the presence of MIP-1alpha ranged from 65-97% at 10 microg/ml Tz, with GM-CFCs being 1.5-4.5-fold more resistant than control cells from the same patient. The highest levels of protection were seen in the GM-CFCs with the highest sensitivity in the absence of MIP-1alpha. Similar degrees of protection were seen for the methylating agent streptozotocin, but no protection was detected for the chloroethylating agents carmustine or mitozolomide in the samples for which there was protection against the toxic effects of Tz. Whereas the mechanism of this effect remains to be established, the results may have potential immediate clinical application in the attenuation of hematological toxicity after administration of methylating antitumor agents.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Division-
dc.subject.meshCell Survival-
dc.subject.meshChemokine CCL3-
dc.subject.meshChemokine CCL4-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshDacarbazine-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshMacrophage Inflammatory Proteins-
dc.subject.meshStreptozocin-
dc.titleMacrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Medical Oncology, Manchester, United Kingdom. markclemons@sprint.caen
dc.identifier.journalClinical Cancer Researchen
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