Antiproliferative effects of suramin on lymphoid cells

Abstract

Suramin, a polyanionic drug used in the treatment of Rhodesian and Gambian trypanosomiasis and more recently in the acquired immune deficiency syndrome, is a potent inhibitor of the constitutive mammalian DNA polymerases alpha, beta, and gamma and the lymphoid-specific polymerase terminal deoxynucleotidyl transferase. To define the effect of this inhibition on cell proliferation, we studied the effect of suramin on several cell lines in culture and in mice in vivo. Suramin, at 200 micrograms/ml (which is regularly achieved in the plasma of patients), had no effect on the proliferation of 4 of 5 nonlymphoid cell lines. In contrast, exposure of 10 lymphoid cell lines to 200 micrograms/ml suramin for 4 days caused significant growth inhibition in 8 of these 10 lines. Suramin given i.p. to BALB/cBYJ mice at clinically relevant doses (15-60 mg/kg) caused profound and prolonged thymic atrophy within 5-7 days of drug administration (greater than a 90% weight loss in mice treated with 60 mg/kg). Thymic sections revealed severe cortical loss, prominence of dendritic cells, and vacuolated macrophages. Liver, peripheral blood, spleen, kidney, and total body weights were not affected. The apparent selective lymphocytotoxicity of suramin may represent an important property of this drug. We speculate that this may account for the persistent immune suppression reported in suramin-treated acquired immune deficiency syndrome patients.