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Articles

Localized Changes in Blood-Brain Barrier Permeability following the Administration of Antineoplastic Drugs

Lindsay A. MacDonell, Pamela E. Potter and Ronald A. Leslie
Lindsay A. MacDonell
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Pamela E. Potter
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Ronald A. Leslie
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DOI:  Published September 1978
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Abstract

The effects of four antineoplastic drugs on the permeability of the blood-brain barrier to Evans blue-albumin and to horseradish peroxidase were studied in cats. Extravasation of tracer in brain tissue was observed only rarely following the injection of methotrexate, cyclophosphamide, or vincristine. However, 5-fluorouracil (15 mg/kg) caused localized Evans blue-albumin exudation in various gray and white matter areas in 8 of 13 cats to which the Evans blue was administered 7 hr after the drug injection. Electron microscopy revealed that 5-fluorouracil stimulated pinocytotic vesicular transport of peroxidase across brain capillary endothelial cells and possibly that it widened endothelial tight junctions. Barrier leakage was not observed when time periods longer than 7 hr elapsed between 5-fluorouracil injection and tracer administration, and extravasation occurred only once after a shorter time interval. These results suggest that changes in bloodbrain barrier permeability observed 7 hr after 5-fluorouracil administration are reversible and of fairly short duration. Such changes may be relevant to the development of secondary intracranial tumors following antineoplastic chemotherapy.

Footnotes

  • ↵1 This work was supported by the Medical Research Council of Canada (MA-5779).

  • ↵3 To whom requests for reprints should be addressed.

  • Received February 28, 1978.
  • Accepted June 13, 1978.
  • ©1978 American Association for Cancer Research.
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September 1978
Volume 38, Issue 9
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Localized Changes in Blood-Brain Barrier Permeability following the Administration of Antineoplastic Drugs
Lindsay A. MacDonell, Pamela E. Potter and Ronald A. Leslie
Cancer Res September 1 1978 (38) (9) 2930-2934;

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Localized Changes in Blood-Brain Barrier Permeability following the Administration of Antineoplastic Drugs
Lindsay A. MacDonell, Pamela E. Potter and Ronald A. Leslie
Cancer Res September 1 1978 (38) (9) 2930-2934;
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Cancer Research Online ISSN: 1538-7445
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