Inhibition by Ionophore A23187 of the Cytotoxicity of Vincristine, Colchicine and X-Rays to Leukemic Lymphocytes

Abstract

The ionophore A23187 was tested for its effect on the sensitivity of normal and leukemic lymphocytes to colchicine, vincristine, and X-irradiation. The ionophore was used because it transfers divalent cations through biological membranes and causes the transformation of normal lymphocytes. The sensitivity of the cells was measured by incubation of lymphocyte suspensions with and without reagent at 37°C for one to seven days and counting the number of viable lymphocytes before and after incubation. Viability of the cells was judged by cytologic criteria as visualized by phase contrast microscopy. Lymphocytes were obtained from patients with chronic lymphocytic leukemia and from normal persons. Colchicine and vincristine killed in one day non-dividing leukemic lymphocytes .while normal lymphocytes were much less sensitive to the two alkaloids. X-irradiation (1000 rad) killed nearly all leukemic lymphocytes in two days and normal lymphocytes in three days. lonophore A23187 (2 × 10^––5M) was moderately toxic to normal but not to leukemic lymphocytes and caused the transformation of both types of cells. The ionophore inhibited the cytocidal action of colchicine and vincristine to leukemic but not to normal lymphocytes and inhibited the action of X-irradiation to both types of lymphocytes. The present findings and a review of the literature suggest the hypothesis that calcium or other divalent ions are involved in the cytotoxicity of colchicine, vincristine, and X-irradiation of leukemic lymphocytes and that there may be an abnormality of the metabolism of divalent ions in leukemic lymphocytes.