This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clemons, M. Articles by Margison, G. Search for Related Content PubMed PubMed Citation Articles by Clemons, M. Articles by Margison, G.

Macrophage Inflammatory Protein 1 Attenuates the Toxic Effects of Temozolomide in Human Bone Marrow Granulocyte- Macrophage Colony-forming Cells¹

Cancer Research Campaign Section of Genome Damage and Repair [M. C., A. W., G. M.], Cancer Research Campaign Department of Medical Oncology [M. C., A. H.], and Cancer Research Campaign Section of Haemopoietic Cell and Gene Therapeutics [C. H., T. M. D., B. L., N. T.], Paterson Institute for Cancer Research, and Department of Pathology, Christie Hospital [J. C.], Manchester M20 4BX, United Kingdom

Macrophage inflammatory protein 1 (MIP-1) 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-1 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 µg/ml Tz]. However, in all 16 cases, MIP-1 (50 ng/ml) protected against GM-CFC killing: survival in the presence of MIP-1 ranged from 65–97% at 10 µg/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-1. 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.

This article has been cited by other articles:

				M. E. Trudeau, M. Crump, D. Charpentier, L. Yelle, L. Bordeleau, S. Matthews, and E. Eisenhauer Temozolomide in metastatic breast cancer (MBC): a phase II trial of the National Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG) Ann. Onc., June 1, 2006; 17(6): 952 - 956. [Abstract] [Full Text] [PDF]