Thymidine as a Chemotherapeutic Agent: Sensitivity of Normal Human Marrow, Peripheral Blood T Cells, and Acute Nonlymphocytic Leukemia

Abstract

Normal marrow granulocyte (CFU-GM) and peripheral blood T-lymphocyte (CFU-TL) colony-forming cells were studied for their sensitivity to high concentrations of thymidine (dThd) and compared to leukemic CFU from patients with acute nonlymphocytic leukemia (ANLL). The sensitivity of two ANLL cell lines was also assessed. dThd was toxic to both CFU-GM and CFU-TL at concentrations above 10(-5) M when cultured under conditions where dThd exposure was analogous to that used in clinical trials. There was little variation in the fractional colony survival between marrow samples, and the sensitivity of CFU-GM closely approximated that of CFU-TL. Thymine was not toxic at up to 10(-3) M. In liquid culture, T cells in G0 at the start of exposure were able to proliferate in the presence of 10(-3) M dThd, whereas T cells already proliferating in response to phytohemagglutinin (PHA) at the start of dThd exposure were killed. Leukemic CFU demonstrated marked variability in dThd sensitivity; blasts from some patients were resistant to dThd, while others were greater than 100-fold more sensitive than normal CFU-GM.