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Thymidine and hypoxanthine requirements of normal and malignant human cells for protection against methotrexate cytotoxicity

By Stephen B. Howell, Susan J. Mansfield and Raymond TaetleContact The Aacr Publications, Stephen B. Howell, Susan J. Mansfield and Raymond Taetle

Abstract

The thymidine (dThd) and hypoxanthine (Hyp) requirements for protection of normal human granulocyte-macrophage col ony-forming units, B-, and T-cells against methotrexate-induced inhibition of proliferation were compared to require ments of three malignant solid-tumor cell lines recently estab lished from human tumor xenografts and of the CCRF-CEM T-cell leukemia. In the presence of excess Hyp, the concentration of dThd that provided 50 % protection (PC50) was 0.2 JUMfor granulocyte-macrophage colony-forming units and normal T-cells; the dThd PC50for malignant cells was five- to seven-fold higher, while that for B-cells was 10- to 40-fold higher. An accurate Hyp PC50 for granulocyte-macrophage colony-form ing units could not be established; however, the Hyp PC50 for T-cells was 0.8 ¡IM,while that for malignant cells was four t

Year: 1981
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