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Membrane and cytoplasmic changes in 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and resistant human malignant glioma-derived cell lines

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Abstract

Human glioma-derived cell lines previously determined by a microtiter chemotherapy assay to be either ‘sensitive’ or ‘resistant’ to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were treated with BCNU (1–80 µg/ml) and observed using microcinematography, scanning electron microscopy, and transmission electron microscopy. Striking bleb formation and cell retraction were observed to occur in a dose-dependent relationship within minutes in the cells known to be BCNU-sensitive. At 15µg/ ml, 69% of cells showed blebs by 30 min, 87% by 90 min, and 100% by 4 hr. This activity was not seen in BCNU-resistant cells. These morphological changes occur at a time too early to be accounted for by the known BCNU mechanism of DNA alkylation and cross-link formation and suggest that cytoplasmic and/or membrane events may be significant initial events in the cytotoxic actions of BCNU.

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Authors and Affiliations

  1. Surgical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

    Barry H. Smith, Margaret Vaughan, Mary Ann Greenwood, Paul L. Kornblith, Allen Robinson, Nobuyuki Shitara & Paul E. McKeever

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  1. Barry H. Smith
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  2. Margaret Vaughan
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  3. Mary Ann Greenwood
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  4. Paul L. Kornblith
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  5. Allen Robinson
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  6. Nobuyuki Shitara
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  7. Paul E. McKeever
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Additional information

Address for reprints: Barry H. Smith, M.D., Ph.D., Surgical Neurology Branch, NINCDS, NIH, Bldg. I OA, Rm. 3E68, Bethesda, MD 20205, USA

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Smith, B.H., Vaughan, M., Greenwood, M.A. et al. Membrane and cytoplasmic changes in 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and resistant human malignant glioma-derived cell lines. J Neuro-Oncol 1, 237–248 (1983). https://doi.org/10.1007/BF00165608

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  • DOI: https://doi.org/10.1007/BF00165608

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