Modulation by taurine of the toxicity of taumustine, a compound with antitumor activity

The antitumor activity of 2-[bis-(2-chloroethyl)-amino]ethanesulfonic acid (also referred to here as "taurine mustard" or "taumustine") was evaluated in the murine P388 and L1210 lymphocytic leukemias and in the pigmented and nonpigmented B16 melanoma systems. Treatment with a single ip dose of taumustine (40 mg/kg) resulted in a 130% increase in life-span for mice bearing P388 (intraperitoneal), a 93% increase for mice bearing L1210 (intraperitoneal), and an approximately 80% increase for mice bearing B16 melanoma (intraperitoneal). Repeated low doses (10 mg/kg) of taumustine promoted a 250% increase in life-span for mice bearing P388 (intraperitoneal), the absence of ascitic fluid from day 4 onward, and the presence of pulmonary emboli from day 5 onward. The inclusion of taurine (5 mM) in the culture medium of P388 cells in primary culture for 45 hours did not alter the cytotoxicity of taumustine, and pretreatment of the tumor-bearing host with taurine (250 mg/kg) in daily treatments with taumustine for up to 8 days did not interfere with antitumor activity (140-160% increased life-span). However, treatment of tumor-bearing mice with taurine abrogated neurotoxicity, intestinal necrosis, pulmonary emboli formation, and tail vein necrosis due to the administration of taumustine. The modulation by taurine of taumustine activity suggests that the combination of these agents offers an advantage of selectivity and host protection during chemotherapy.