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
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↵1 This work was supported by the Medical Research Council of Canada (MA-5779).
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↵3 To whom requests for reprints should be addressed.
- Received February 28, 1978.
- Accepted June 13, 1978.
- ©1978 American Association for Cancer Research.
Volume 38, Issue 9
