5'-DEOXY-5-FLUOROURIDINE SELECTIVE TOXICITY FOR HUMAN-TUMOR CELLS COMPARED TO HUMAN-BONE MARROW

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (6) , 2525-2528
Abstract
Studies were completed to establish the comparative cytotoxicity of 5''-deoxy-5-fluorouridine (5''-dFUrd) and other fluoropyrimidines in human bone marrow stem cells and several cultured human tumor cell lines. In vitro clonogenic assays were used to measure cytotoxicity following a 3-h drug exposure. 5''-dFUrd was less potent than was 5-fluorouracil or 5-fluoro-2''-deoxyuridine in all cells examined, exhibiting its best activity against the 47-DN [concentration that prevented 50% clonal growth compared to untreated control (LD50) = 32 .mu.M] and MCF-7 (LD50 = 35 .mu.M) breast carcinomas and MG-63 osteosarcoma (LD50 = 41 .mu.M). Intermediate activity was observed against HCT-8 (LD50 = 200 .mu.M) and Colo-357 (LD50 = 150 .mu.M) gastrointestinal tumors. 5''-dFUrd had very poor activity against the HL-60 leukemia (LD50 = 470 .mu.M). The suppression of the clonal growth of human bone marrow stem cells required the greatest amount of 5''-dFUrd (LD50 = 580 .mu.M). With use of these studies, a therapeutic ratio (concentration that prevented 25% clonal growth compared to untreated control of bone marrow divided by LD50 of tumor) was calculated for each drug in each tumor. 5''-dFUrd had values ranging from 1.2 to 7.5 for the solid tumors and 0.5 in HL-60 cells. This was in marked contrast to 5-fluorouracil, or 5-fluoro-2''-deoxyuridine, which failed in all cases to have ratios .gtoreq. 1. 5''-dFUrd can exhibit a cytotoxic selectivity for human tumor cells compared to human bone marrow stem cells that does not exist for 5-fluorouracil or 5-fluoro-2''-deoxyuridine. 5''-dFUrd may be of greater therapeutic benefit in the treatment of certain human cancers than the fluoropyrimidines used currently.

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