EFFECTS OF CHEMOTHERAPEUTIC DRUGS ON PLATELET AND METASTATIC TUMOR CELL-ENDOTHELIAL CELL-INTERACTIONS AS A MODEL FOR ASSESSING VASCULAR ENDOTHELIAL INTEGRITY

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (1) , 331-336
Abstract
An in vitro assay for examining the sublethal effects of chemotherapeutic agents on vascular endothelial integrity was described. Using vascular endothelial cell monolayers [from humans], the kinetics of binding of radiolabeled platelets or metastatic tumor cells [mouse B16 cell] were altered when endothelial cells were pretreated for 2 h with low, clinically relevant concentrations of certain drugs. EM examination by scanning electron microscopy revealed these same drugs caused endothelial cell retraction and exposure of subendothelial matrix. Platelets and tumor cells were found bound only to the exposed areas of subendothelial matrix. Some drugs (bleomycin, 1,3-bis(2-chloroethyl)-1-nitrosourea, vincristine) induced rapid endothelial cell retraction and increased platelet and tumor cell binding to exposed subendothelial matrix, while 1 of the drugs tested (Adriamycin) caused delayed (1-3 days after a 2-h drug treatment) endothelial cell retraction and increased cell binding. Of the drugs tested, only 5''-fluoro-2''-deoxyuridine which interferes with DNA replication failed to induce endothelial cell retraction and increased tumor cell and platelet binding. Certain drug effects on the vascular endothelium can be assessed using the vascular endothelial cell monolayer model.