1985 Volume 76 Issue 1 Pages 68-74
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 100μg/ml (as the cisplatin-equivalent concentration) was less than that of cisplatin at 0.125μg/ml. The prepared protein-bound platinum exhibited antitumor activity against colon adenocarcinoma 26 in mice, when administered iv daily for 9 consecutive days at 32 and 64mg/kg (as the cisplatin-equivalent dose). Cisplatin similarly administered exhibited antitumor activity at daily doses of only 1 and 2mg/kg. Administration of the protein-bound platinum at such high doses as 32 and 64mg/kg (as the cisplatin-equivalent dose) caused elevation of serum BUN and reduction of bone marrow cells in mice. After iv administration of cisplatin to mice at 6mg/kg, ultrafiltrable platinum was detected in the plasma for the first 30min. Thereafter platinum was found only in protein-bound form. When mice were iv inoculated with colon adenocarcinoma 26 more than 30min after cisplatin administration, no prolongation of the life span was observed. From these results, it is concluded that mouse serum protein-bound platinum does not contribute significantly to cisplatin antitumor activity and toxicity in mice.
