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The Binding of Vinblastine by Platelets in the Rat¹

Cancer Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

Rats have been given i.p. injections of vinblastine tritiated in the aromatic rings (dose, approximately 0.25 mg/kg). The isotope levels in the blood were measured over a 24-hr period. The peak radioactivity was reached 1.5 hr after the injection, at which time approximately 2% of the dose was present in the circulation. In this early period, most of the radioactivity was found in the buffy coat. Blood smears of rats given tritiated vinblastine were examined autoradiographically with a "drytransfer" method developed to minimize translocation of soluble radioactive compounds. Most of the silver grains in the autoradiograms were associated with single platelets and platelet clumps; leukocytes were only slightly labeled and red cells negligibly labeled. Blood, collected 2 hr after the tritiated alkaloid was injected i.p., was fractionated by differential centrifugation. The distribution of radioactivity was approximately: plasma, 15%; red cells, 10%; leukocytes, 15%; platelets, 60%. Isotopic dilution analysis showed that unchanged vinblastine accounted for essentially all the platelet radioactivity but for only about 50% of that in the plasma. In vitro, when platelet-rich plasma was incubated with tritiated vinblastine (0.05 µg/ml plasma), 75% of the radioactivity was taken up by the platelets. It is suggested that platelets may play a role in mediating the chemotherapeutic action and pharmacological activity of the Vinca alkaloids.

¹ This investigation was supported by grants from the Medical Research Council of Canada and the National Cancer Institute of Canada.

Received 10/ 6/69. Accepted 1/15/70.

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