Resistance in Leukemic Cells to a Guanine Analog, 8-Azaguanine

Abstract

The development of resistance in a transplantable acute lymphocytic leukemia of the mouse to a guanine analog, 8-azaguanine, is reported. Optimal growth of the resistant cells is attained in mice receiving near maximum tolerable doses of 8-azaguanine, indicating partial dependence of the variant line on the analog used in developing resistance. The sensitive (control) line of leukemia has shown nearly complete inhibition of tumor growth at comparable transfer generations. A-methopterin and 2,4,6-triethylene imino-s-triazine inhibit growth of the resistant line. The biologic behavior of resistant leukemic cells grown in mice receiving 8-azaguanine strikingly resembles sensitive cells grown in antagonist-free mice: A florid leukemia develops with leukocytosis and escape of lymphoblasts into the blood, severe infiltration into lymph nodes, spleen and liver, resulting in death at approx. the same time as controls.