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% NaCl 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 suppression 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.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine; D004912:Erythrocytes / Q000032:analysis*; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D008935:Mitoguazone / Q000008:administration & dosage; D009374:Neoplasms, Experimental / Q000378:metabolism; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D010976:Platelet Count; D011073:Polyamines / Q000032:analysis* / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344
D011073:Polyamines; D009952:Ornithine; D008935:Mitoguazone; D000518:Eflornithine