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" Effects of ionophore copolymers on the growth and differentiation of the HL60 promyelocytic cell line "
M. H. Al-Qawasmeh
R. L. C. Hunter, Irene J.
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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1112659
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| Doc. No
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TLpq303622217
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| Main Entry
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M. H. Al-Qawasmeh
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R. L. C. Hunter, Irene J.
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| Title & Author
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Effects of ionophore copolymers on the growth and differentiation of the HL60 promyelocytic cell line\ M. H. Al-QawasmehR. L. C. Hunter, Irene J.
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| College
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Emory University
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| Date
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1987
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| student score
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1987
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| Degree
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Ph.D.
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| Page No
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182
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| Abstract
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Reverse octablock copolymers are amphiphilic compounds composed of an ethylenediamine central initiator and blocks of hydrophilic polyoxyethylene and hydrophobic polyoxypropylene. They have monovalent cation ionophore activity on artificial membranes and human red blood cells. A promyelocytic cell line, HL60, is an established model for studying hematopoietic cell differentiation. HL60 cells are multipotent: some agents induce them to undergo monocytic differentiation, while others induce myeloid or eosinophilic differentiation. Using H-thymidine incorporation each copolymer inhibited DNA synthesis. Inhibition varied among the copolymers, was dose-dependent, and increased with time. No simple relationships between the inhibitory activity of each copolymer and its ionophore activity or other physicochemical property were observed. Most of the copolymers followed the pattern of toxicity observed in other systems. However, one copolymer, T130R2, was much less toxic than expected. It also was the most potent ionophore. After establishing that lactate dehydrogenase (LDH) content correlates well with cell number, lytic activity of copolymers, especially T130R2, was not sufficient to explain the inhibition of DNA synthesis. Several copolymers arrest DNA synthesis. Their potency in this assay was a direct function of their ionophore activity. T130R2 was the most potent inhibitor. The relative number of cells in each phase of the cell cycle was estimated from the fluorescence of propidium iodide labeled copolymer-treated cells using flow cytometry. T130R2 blocked the HL60 cells between G and S. I observed a decrease in the total number of cells but an increased proportion of adherent cells in T130R2-treated cultures. This was quantitated by measuring the LDH content of adherent and non-adherent cells. T130R2 inhibits cellular proliferation by inducing differentiation. Using a panel of differentiation markers confirmed T130R2 induced HL60 to undergo monocytic/macrophage differentiation. Using morphology, adherence and procoagulant expression, concentrations of H-7 and sphinganine which inhibit differentiation induced by TPA had little effect on that induced by T130R2. To investigate the possible role of Na+-dependent H+ efflux in T130R2-induced differentiation, an inhibitor, amiloride was used. It inhibited the differentiation induced by both TPA and T130R2. The dose required to inhibit T130R2-induced differentiation (30 muM) was much higher than that required to inhibit TPA-induced differentiation (1 muM). (Abstract shortened with permission of author.)
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Health and environmental sciences
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Pathology
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