Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity.

Abstract

The purpose of this study was to evaluate the effect of a concomitant infusion of ornithine on the difluoromethylornithine (DFMO)-induced thrombocytopenia and antitumor activity. Male Fischer 344 rats with either a transplantable fibrosarcoma or Ward colon tumor were given a 12-day continuous infusion of DFMO (2000 mg/kg/day) alone or with ornithine. The dose of ornithine was defined as the molar ratio to DFMO. A continuous infusion of DFMO significantly reduced circulating platelet counts to 5-16% of the control. Concomitant ornithine treatment at a molar ratio of 0.2-0.5 resulted in protection of the rat from thrombocytopenia while the antiproliferative activity of DFMO against the fibrosarcoma or Ward colon tumor was unaffected. At a higher ornithine: DFMO molar ratio (0.7), the DFMO-induced inhibition of tumor growth was blocked. Tissue polyamine levels suggest a different sensitivity of tumor and normal tissue to DFMO. Concomitant ornithine resulted in a greater increase in the polyamine levels of normal tissues, compared with the tumor. These results suggest that ornithine can selectively inhibit DFMO-induced thrombocytopenia while not affecting the antitumor activity.

• Authors: V B Grossie Jr, D M Ota, J A Ajani, T H Chang, D Patenia, K Nishioka
• Journal: Cancer research (Cancer Res) Vol. 49 Issue 15 Pg. 4159-62 (Aug 01 1989) ISSN: 0008-5472 [Print] United States
• PMID: 2501023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biogenic Polyamines
• Ornithine
• Eflornithine

Topics

• Animals
• Biogenic Polyamines (analysis)
• Eflornithine (therapeutic use, toxicity)
• Male
• Ornithine (pharmacology)
• Rats
• Rats, Inbred F344
• Sarcoma, Experimental (drug therapy)
• Thrombocytopenia (chemically induced, prevention & control)