ANTITUMOR-ACTIVITY AND TOXICITY OF SERUM PROTEIN-BOUND PLATINUM FORMED FROM CISPLATIN

  • 1 January 1985
    • journal article
    • research article
    • Vol. 76  (1) , 68-74
Abstract
When cisplatin was incubated with mouse serum, its cytotoxicity towards P388 leukemia cells decreased with the formation of non-ultrafiltrable or protein-bound platinum. The cytotoxicity of prepared mouse serum protein-bound platinum at 100 .mu.g/ml (as the cisplatin-equivalent concentration) was less than that of cisplatin at 0.125 .mu.g/ml. The prepared protein-bound platinum exhibited antitumor activity against colon adenocarcinoma 26 in mice, when administered i.v. daily for 9 consecutive days at 32 mg/kg and 64 mg/kg (as the cisplatin-equivalent dose). Cisplatin similarly administered exhibited antitumor activity at daily doses of only 1 mg/kg and 2 mg/kg. Administration of the protein-bound platinum at such high doses as 32 mg/kg and 64 mg/kg (as the cisplatin-equivalent dose) caused elevation of serum BUN [blood urea N) and reduction of bone marrow cells in mice. After i.v. administration of cisplatin to mice at 6 mg/kg, ultrafiltrable platinum was detected in the plasma for the 1st 30 min. Thereafter platinum was found only in protein-bound form. When mice were i.v. inoculated with colon adenocarcinoma 26 > 30 min after cisplatin administration, no prolongation of the life span was observed. It is concluded that mouse serum protein-bound platinum does not contribute significantly to cisplatin antitumor activity and toxicity in mice.