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The Effect of Heparin on the Cytotoxicity and Uptake of Anti-neoplastic Drugs in Cultured Burkitt Lymphoma Cells¹

Departments of Internal Medicine, Chemotherapy Unit [R. W., F. B.], and Pharmacology [R. R.], The University of Michigan Medical Center, Ann Arbor, Michigan 48104

Preliminary clinical studies have been reported suggesting an increased response rate to a five-drug combination program in lung cancer patients who were anticoagulated with heparin. This study was undertaken to determine the effect of heparin on the cytotoxicity and cellular drug uptake of four antineoplastic agents. Burkitt lymphoma cells (P₃J) in continuous culture were incubated with heparin in a concentration of 0.5 unit/ml for 0 or 72 hr prior to the addition of radioisotopically labeled nitrogen mustard, methotrexate, 6-mercaptopurine, or 5-fluorouracil. Cytotoxicity and cellular drug uptake were then determined.

Heparin alone had no effect on cell growth, viability, or DNA synthesis, as measured by thymidine-³H incorporation, during the log phase of culture growth over 72 hr. The cytotoxic effect of the four antitumor drugs also was not altered by incubating the cells with heparin for 0 or 72 hr. The uptake of the radioactively labeled agents in heparin-treated cultures was not significantly different from that of control cultures.

¹ Supported in part by Institutional Research Grant IN-40N to the University of Michigan from the American Cancer Society and by Grant CA-12765 from the National Cancer Institute.

² Supported by USPHS Cancer Training Grant T12CA05098-07.

³ To whom requests for reprints should be sent.

Received 5/30/74. Accepted 8/13/74.