Red blood cell polyamine levels and host toxicity during continuous alpha‐difluoromethylornithine infusion

The dose effects of continuous alpha‐difluoromethylornithine (DFMO) infusion on red blood cell (RBC) polyamine levels, host toxicity and tumor growth were determined. Male rats with and without a transplantable methylcholanthrene‐induced sarcoma received intravenously either 0.45% NaCI or DFMO at 500 mg, 1,000 mg, or 2,000 mg/kg body wt/day for 6 or 12 days. Dose‐related inhibition of tumor growth was noted after the 12‐day treatment. There were no changes in host carcass weight, food intake, plasma albumin, hematocrit or white blood cell counts. Platelet supression was associated with the 1,000‐ and 2,000‐mg doses with the 12‐day treatment. Morphometry of the small intestine revealed mild but significant shortening of villi in the duodenum and jejunum at the 2,000‐mg dose, but none of the animals developed diarrhea. The 500‐mg DFMO dose reduced the rate of tumor growth without inducing platelet suppression or altering intestinal morphology. A decrease in RBC putrescine levels was noted at all doses. RBC spermidine levels increased with the 500‐mg dose. RBC spermine levels were higher at all doses compared with controls. These results suggest that thrombocytopenia is the major dose‐limiting side‐effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day.