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

Publication ,  Journal Article
Grossie, VB; Ota, DM; Ajani, JA; Chang, TH; Patenia, D; Nishioka, K
Published in: Cancer Res
August 1, 1989

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 1, 1989

Volume

49

Issue

15

Start / End Page

4159 / 4162

Location

United States

Related Subject Headings

  • Thrombocytopenia
  • Sarcoma, Experimental
  • Rats, Inbred F344
  • Rats
  • Ornithine
  • Oncology & Carcinogenesis
  • Male
  • Eflornithine
  • Biogenic Polyamines
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Grossie, V. B., Ota, D. M., Ajani, J. A., Chang, T. H., Patenia, D., & Nishioka, K. (1989). Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity. Cancer Res, 49(15), 4159–4162.
Grossie, V. B., D. M. Ota, J. A. Ajani, T. H. Chang, D. Patenia, and K. Nishioka. “Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity.Cancer Res 49, no. 15 (August 1, 1989): 4159–62.
Grossie VB, Ota DM, Ajani JA, Chang TH, Patenia D, Nishioka K. Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity. Cancer Res. 1989 Aug 1;49(15):4159–62.
Grossie, V. B., et al. “Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity.Cancer Res, vol. 49, no. 15, Aug. 1989, pp. 4159–62.
Grossie VB, Ota DM, Ajani JA, Chang TH, Patenia D, Nishioka K. Reduction of difluoromethylornithine-induced thrombocytopenia in rats with ornithine while maintaining antitumor activity. Cancer Res. 1989 Aug 1;49(15):4159–4162.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 1, 1989

Volume

49

Issue

15

Start / End Page

4159 / 4162

Location

United States

Related Subject Headings

  • Thrombocytopenia
  • Sarcoma, Experimental
  • Rats, Inbred F344
  • Rats
  • Ornithine
  • Oncology & Carcinogenesis
  • Male
  • Eflornithine
  • Biogenic Polyamines
  • Animals