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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abraham, N. G. Articles by Levere, R. D. Search for Related Content PubMed PubMed Citation Articles by Abraham, N. G. Articles by Levere, R. D. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Microenvironmental toxicity of azidothymidine: partial sparing with hemin NG Abraham, D Bucher, U Niranjan, AC Brown, JD Lutton, A Distenfeld, T Ahmed and RD Levere Department of Medicine, New York Medical College, Valhalla, NY 10595. Azidothymidine (AZT) is a useful drug in management of AIDS. Nevertheless, its hematologic toxicity such as anemia and neutropenia present further complications to an already compromised hematopoietic state in patients. We studied the effects of AZT on human and murine bone marrow (BM) colony growth as determined by assays of CFU-E, BFU-E, CFU-GM, and fibroblastoid stromal (CFU-Fb) colonies. Cultures were grown in methylcellulose with growth factors and scored after three- to 14-day incubation. In general, murine marrow cultures were more sensitive to AZT as compared with human marrow. Furthermore, interindividual variation in toxicity to AZT was observed between marrow samples; 1 mumol/L AZT inhibited murine CFU-E, BFU-E, and CFU-GM by 98% to 100%, whereas human marrow was inhibited by 52%, 87%, and 65%, respectively. Lower concentrations of AZT (0.1 mumol/L) inhibited murine erythroid colony growth by 85% to 90%, whereas human growth was inhibited by only 39% to 52%. Myeloid colony inhibition was similar for human and murine systems. CFU-Fb growth was markedly suppressed (75%) by 1 mumol/L AZT. Hemin, at a concentration of 10 mumol/L, overcame some of the inhibitory effects of 1 to 0.1 mumol/L AZT without hindering antiviral activity. Inhibition of human CFU-E growth was completely overcome with hemin, whereas CFU-GM growth was recovered to 66% to 74% of control. A similar but less pronounced effect was observed for BFU-E. Furthermore, hemin does not decrease AZT's effects of HIV antigen content in vitro. We conclude that anemia and neutropenia, occurring as a result of AZT, may not be as pronounced in the presence of hemin. Furthermore, CFU-Fb was significantly reduced in the presence of low concentrations of AZT. This may indicate a major target site for BM toxicity since the stromal microenvironment may be responsible for maintaining short- and long-term hematopoiesis. Volume 74, Issue 1, pp. 139-144, 07/01/1989 Copyright © 1989 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF] L. Gribaldo, I. Malerba, A. Collotta, S. Casati, and A. Pessina Inhibition of CFU-E/BFU-E by 3'-Azido-3'-deoxythymidine, Chlorpropamide, and Protoporphirin IX Zinc (II): A Comparison between Direct Exposure of Progenitor Cells and Long-Term Exposure of Bone Marrow Cultures Toxicol. Sci., November 1, 2000; 58(1): 96 - 101. [Abstract] [Full Text] [PDF]

	Copyright © 1989 by American Society of Hematology         Online ISSN: 1528-0020