STUDIES ON ANTITUMOR DRUGS——ⅩⅦ.INFLUENCE OF Sb-71 ON INCORPORATION OF Zn~(65)INTO TUMOR CELLS IN MICE BEARING EHRLICH ASCITES CARCINOMA

The study of structure-activity relationship of Sb-complexones showed that the bound form of Sb-chelating compound such as Sb-71 produced more marked antitumor effect. It has been reported that the growth of malignant tumors is closely associated with the metabolism of trace metals; this metabolism can be altered by metal chelates. In this paper the action of Sb-71 and its analogs on incorporation of Zn⁶⁵ into tumor cells was investigated. Zn⁶⁵C1₂ was injected intraperitoneally to mice bearing Ehrlich ascites carcinoma. The radioactivity was measured by means of counter and MC-4 countertube. The total protein nitrogen was determined by the modified micro-Kjeldahl method and Biuret method. Experiments were performed both in vitro and in vivo. 1. In vitro experiments showed that Sb-71 and other compounds such as ATA, EDTA-HgNa⁺, EDTA-BiNH₄⁺, EDTA-PbNH₄⁺, EDTA-SnNH₄⁺ and EDTA-BaBa⁺⁺ produced definite inhibition on Zn⁶⁵ incorporation into tumor cells by 22—60%. ATA and Sb-71 (antimony ammonia triacetic acid) exhibited more marked effects, whilst tartar emetic had none. 2. In mice, a single intraperitoneal injection of 30mg/kg of Sb-71 caused a marked depression on Zn⁶⁵ incorporation into tumor cells. The maximal action was attained 5—7 hours after injection; meanwhile, the radioactivity of nucleo-protein was decreased significantly. Twelve hours later the inhibitory effect subsided. Under the influence of the drug, the incorporation of Zn⁶⁵ into liver protein was unchanged. It suggests that the action of Sb-71 has some selectivity to tumor cells. The intraperitoneal injection of ATA did not produce inhibition of Zinc incorporation into tumor cells, but promoted the removal of Zn⁶⁵ from the ascitic fluid. 3.In mice bearing Ehrlich ascites carcinoma, after intraperitoneal injection of EDTA-HgNa⁺(4mg/kg), EDTA-BiNH₄⁺ (10 mg/kg) or EDTA-PbNH₄⁺ (200 mg/kg), all of them except EDTA-HgNa⁺, did not alter Zn⁶⁵ incorporation into tumor cells as compared with control groups.